Injerto osteocondral congelado para tratamiento de lesiones de cartílago de rodilla: resultados a 7 años de seguimiento / Use of frozen osteochondral allograft for the treatment of cartilage defects of the knee. Results at seven-year follow-up

Resumen Introducción : Las lesiones osteocondrales de rodilla son una afección frecuente en jóvenes. Los trasplantes alogénicos usando injerto congelado se presentan como una opción de tratamiento en pacientes con lesiones grandes o sin zona dadora. Este trabajo buscó analizar retrospectivamente los resultados funcionales y la tasa de falla de los trasplantes osteocondrales con injerto cadavérico congelado. Métodos : Se incluyeron pacientes sometidos a tras plantes osteocondrales de rodilla con injerto cadavérico congelado en nuestra institución, entre 2014 y 2019, con dos años de seguimiento mínimo. Variables evaluadas: edad al momento de la intervención, escalas funciona les International Knee Documentation Committee (IKDC) y Lysholm pre y post operatorios, complicaciones y tasa de falla. Resultados : Incluimos 25 pacientes. La edad media fue de 43.5 años (RIQ 29-50), 45% fueron mujeres y el seguimiento promedio fue de 83 meses (DS 54.6). El ta maño promedio del defecto osteocondral fue de 4 cm2. La escala de Lysholm promedio pre y postoperatorio fue de 39 (DS 19.3) y 82 (DS 15.4) respectivamente (p < 0.01). El IKDC promedio pre y postoperatorio fue de 42 (DS 13.8) y 60 (DS 13.5) respectivamente (p < 0.01). La tasa de falla fue del 20% (n=5). Discusión : Los pacientes presentaron una mejoría postoperatoria evidenciada en los resultados funcio nales, y una tasa de falla del 20%. El uso de trasplante osteocondral congelado se presenta como un recurso útil para el tratamiento de lesiones condrales graves.

Abstract Introduction : Knee osteochondral lesions represent a frequent pathology within young active patients. One possible indication for severe lesions or in case of im possibility of harvesting an autograft is the use of fresh frozen allograft. The objective of this study was to ret rospectively analyze functional results and failure rate after osteochondral transplants using fresh frozen al lografts. Methods : We analyzed data from patients who under went knee osteochondral transplant using mosaicplasty technique with fresh frozen allografts at our institution between 2014 and 2019. We included those patients with at least two-year follow-up. Demographic characteristics such as age at the moment of intervention and size of the defect were included. Functional results were assessed using pre and postoperative Lysholm and IKDC scores. Patients who underwent a knee replacement were considered failures. Results : Twenty-five patients were included. The me dian age was 43.5 years (IQR 29-50), 45% were female and the mean follow-up was 83 months (SD 54.6). Mean osteochondral defect size was 4 cm2. Mean pre and post operative Lysholm scores were 39 (SD 19.3) and 82 (SD 15.4) respectively (p < 0.01). Mean pre and postoperative IKDC scores were 42 (SD 13.8) and 60 (SD 13.5) respec tively (p < 0.01). Five patients (20%) underwent a knee replacement afterwards and were considered failures. Discussion : Our results after a mean seven-year follow-up evidenced an overall improvement in func tional scores and a failure rate of 20%. Osteochondral transplant using fresh frozen allografts is a reliable and feasible treatment for patients with large osteochondral defects.

Updates in the Treatment of Knee Osteoarthritis / Atualizações no tratamento da osteoartrite de joelho

Abstract Knee osteoarthritis (OA) is an inflammatory and degenerative condition resulting in articular cartilage destruction and functional loss. Its prevalence has grown considerably due to increased life expectancy and obesity, and its diagnosis relies on evaluation, medical examination, and confirmation by supplementary radiographic images. Knee OA is multifactorial and influenced by several local, systemic, and external aspects. In addition, its progress and therapeutic responses highly depend on the characteristics of each subject. The initial recommendation is drug treatment and alternative therapies to improve quality of life. However, if these treatments are unsuccessful, one must consider surgical treatment. Surgical options include arthroscopies, osteotomies, and partial and total arthroplasties, while non-surgical treatments include medications and alternative therapies such as infiltrations, acupuncture, and physical exercise. It is worth highlighting that biomarkers can be a significant strategy for early disease detection, assessment of disease activity, prediction of prognosis, and monitoring a better response to therapy. Nevertheless, this topic must be the focus of further research to confirm its findings.

Resumo A osteoartrite (OA) do joelho é uma doença inflamatória e degenerativa que ocasiona a destruição da cartilagem articular e leva à perda de funções. Sua prevalência vem crescendo consideravelmente devido ao aumento da expectativa de vida e da obesidade, e o diagnóstico pode ser feito por meio de avaliação e exames médicos, e é confirmado em imagens radiográficas complementares. Uma condição multifatorial, a OA do joelho pode ser influenciada por diversos aspectos locais, sistêmicos e externos; além disso, a sua evolução e as respostas aos tratamentos dependem muito das características de cada indivíduo. Inicialmente, recomenda-se proceder a um tratamento medicamentoso e a terapias alternativas que melhorem a qualidade de vida do paciente; mas, a partir do momento em que se verifica que tais terapias não estão proporcionando resultados satisfatórios, um tratamento cirúrgico deve ser considerado. Entre os tratamentos cirúrgicos, as artroscopias, as osteotomias e as artroplastias parciais e totais são destacadas; os métodos não cirúrgicos incluem o uso de medicamentos e de terapias alternativas, como infiltrações, acupuntura e prática de exercícios físicos. Vale ressaltar ainda que a utilização de biomarcadores pode ser uma importante estratégia para detectar precocemente a doença, avaliar sua atividade, prever um prognóstico e monitorar uma melhor resposta à terapia; porém, esse tema ainda deve ser foco de mais estudos para que os seus resultados sejam comprovados.

Ejercicio terapéutico en la disminución del dolor en pacientes con artrosis de rodilla grado 1: revisión sistemática / Therapeutic exercise to reduce pain in patients with grade 1 knee arthrosis: systematic review / Exercício terapêutico para reduzir a dor em pacientes com artrose grau 1 do joelho: revisão sistemática

La artrosis de rodilla grado 1 es un problema frecuente a escala mundial. La fisioterapia se presenta como una alternativa prometedora para el tratamiento conservador de esta patología, ya que reduce eficazmente la artralgia. Objetivo. Describir la eficacia de los ejercicios terapéuticos para aliviar el dolor en la artrosis de rodilla grado I. Metodología. Se trata de una revisión sistemática, que abarcó una búsqueda exhaustiva en varias bases de datos como Pubmed, Scielo y Elsevier. Los criterios de búsqueda incluyeron ensayos de control aleatorios, experimentales y cuasiexperimentales realizados entre los años 2017 y 2023. Resultados. De un total de 82 documentos se excluyeron 40 al ser estudios secundarios. Posteriormente, se excluyeron 21 estudios adicionales debido a la escasa relación entre las variables del estudio y a su falta de disponibilidad. Finalmente, se seleccionaron 21 artículos que cumplieron con los criterios de evaluación de calidad metodológica mediante la escala CRF-QS. Para evaluar el dolor, la rigidez, la funcionalidad y la calidad de vida, se utilizaron escalas como EVA, NPRS, WOMAC y OXFORD. Los ejercicios isocinéticos resultaron ser los más efectivos, ya que demostraron un aumento de la fuerza y el grosor del cartílago articular, lo que resultó en una disminución de las puntuaciones de EVA de 8,05 a 3,75. Conclusión. El ejercicio terapéutico supervisado centrado en el fortalecimiento de las extremidades inferiores ha demostrado ser una alternativa efectiva para el tratamiento conservador de la artrosis de rodilla grado I. Este enfoque alivia eficazmente el dolor, mejora la calidad de vida e incluso puede detener la progresión de la enfermedad.

Grade 1 knee osteoarthritis is a common problem worldwide. Physiotherapy is presented as a promising alternative for the conservative treatment of this pathology, since it effectively reduces arthralgia. Aim. To describe the effectiveness of therapeutic exercises to relieve pain in grade I knee osteoarthritis. Methodology. This is a systematic review, which included an exhaustive search in several databases such as Pubmed, Scielo and Elsevier. Search criteria included randomized, experimental and quasi-experimental control trials conducted between the years 2017 and 2023. Results. Of a total of 82 documents, 40 were excluded as they were secondary studies. Subsequently, 21 additional studies were excluded due to poor relationships between study variables and lack of availability. Finally, 21 articles were selected that met the methodological quality evaluation criteria using the CRF-QS scale. To evaluate pain, stiffness, functionality and quality of life, scales such as VAS, NPRS, WOMAC and OXFORD were used. Isokinetic exercises were found to be the most effective, demonstrating an increase in articular cartilage strength and thickness, resulting in a decrease in VAS scores from 8.05 to 3.75. Conclusion. Supervised therapeutic exercise focused on strengthening the lower extremities has been shown to be an effective alternative to the conservative treatment of grade I knee osteoarthritis. This approach effectively relieves pain, improves quality of life, and may even stop the progression of osteoarthritis. disease.

A osteoartrite do joelho grau 1 é um problema comum em todo o mundo. A fisioterapia apresenta-se como uma alternativa promissora para o tratamento conservador desta patologia, uma vez que reduz eficazmente a artralgia. Mirar. Descrever a eficácia dos exercícios terapêuticos no alívio da dor na osteoartrite de joelho grau I. Metodologia. Trata-se de uma revisão sistemática, que incluiu uma busca exaustiva em diversas bases de dados como Pubmed, Scielo e Elsevier. Os critérios de pesquisa incluíram ensaios de controle randomizados, experimentais e quase-experimentais realizados entre os anos de 2017 e 2023. Resultados. De um total de 82 documentos, 40 foram excluídos por se tratarem de estudos secundários. Posteriormente, 21 estudos adicionais foram excluídos devido às más relações entre as variáveis do estudo e à falta de disponibilidade. Por fim, foram selecionados 21 artigos que atenderam aos critérios de avaliação da qualidade metodológica pela escala CRF-QS. Para avaliar dor, rigidez, funcionalidade e qualidade de vida foram utilizadas escalas como VAS, NPRS, WOMAC e OXFORD. Os exercícios isocinéticos foram considerados os mais eficazes, demonstrando um aumento na força e espessura da cartilagem articular, resultando em uma diminuição nos escores VAS de 8,05 para 3,75. Conclusão. O exercício terapêutico supervisionado focado no fortalecimento das extremidades inferiores tem se mostrado uma alternativa eficaz ao tratamento conservador da osteoartrite do joelho grau I. Esta abordagem alivia eficazmente a dor, melhora a qualidade de vida e pode até interromper a progressão da osteoartrite.

The role of PINK1/Parkin-mediated mitophagy in mechanical imbalance-induced endplate cartilage degeneration / 局解手术学杂志

Objective To detect the changes of mitophagy level in rats with endplate cartilage degeneration induced by spinal instability,and explore the role of PINK1/Parkin-mediated mitophagy in endplate cartilage and intervertebral disc degeneration.Methods The rat spinal instability model was established by surgically removing the superspinal and interspinal ligaments of L2 to L5,and cleaning the bilateral articular processes of the L2 to L5.Eighteen SD rats were divided into the normal group,the degenerative group,and the carbonyl cyanide 3-chlorophenylhydrazone(CCCP)group,with 6 rats in each group.The rats in the normal group had no special treatment,the rats in the degenerative group constructed a rat spinal instability model,and the rats in the CCCP group were injected with 5 μL of CCCP(10 μmol/L)in the intervertebral disc after the construction of spinal instability model.The changes of histomorphology in the endplate cartilage and intervertebral disc were abserved by HE staining,and the change of extracellular matrix of endplate cartilage was observed by safranin O-fast green staining.RT-PCR detected the mRNA expression of type Ⅱ collagen(COL-2A),aggrecan(ACAN),PINK1 and Parkin in each group.The changes of the protein expression levels of COL-2A,ACAN,PINK1,Parkin and mitochondrial membrane proteins of Tomm20 and Timm23 were detected by Western blot.Results Compared with the normal group,the intervertebral disc nucleus pulposus of rats in the degenerative group was significantly destroyed and the secretion of extracellular matrix of endplate chondrocytes decreased;while the structure of intervertebral discs for rats in the CCCP group was more intact,and the secretion of extracellular matrix of endplate chondrocytes was significantly increased compared with that in the degenerative group.Compared with the normal group,the expression of COL-2A and ACAN in endplate cartilage tissues of rats in the degenerative group were significantly down-regulated(P<0.05),the expression of mitochon-drial autophagy-related genes of PINK1 and Parkin were significantly decreased(P<0.05),and the expression of mitochondrial membrane proteins of Tomm20 and Timm23 were increased(P<0.05).Compared with the degenerative group,the expression of COL-2A,ACAN,PINKI and Parkin in the endplate cartilage tissue of rats in the CCCP group were significantly up-regulated(P<0.05),and the protein levels of Tomm20 and Timm23 were significantly down-regulated(P<0.05).Conclusion Rat spinal instability leads to a decrease level of mitophagy mediated by PINK1/Parkin signaling pathway in endplate cartilage,thereby inducing endplate cartilage and intervertebral disc degeneration,and the activation of mitophagy can significantly reduce endplate cartilage and intervertebral disc degeneration.

Study of synovial mesenchymal stem cells combined with PRP in cartilage repair / 中国医学装备

Objective:To compare the repair effects of three kinds of treatment methods included synovial mesenchymal stem cells(SMSCs),platelet rich plasma(PRP)and the combination of them with knee joint cavity injection on cartilage injury of rabbit.Methods:A total of 24 New Zealand rabbits were selected to establish a cartilage injury model of knee joint by using surgery in knee joint of them.The rabbits with cartilage injury model were divided into four groups using a random number table method,which included blank group,single SMSCs with joint cavity injection group(SMSCs group),PRP with joint cavity injection group(PRP group)and the combination of SMSCs and PRP with joint cavity injection group(SMSCs+PRP group),with 6 rabbits in each group.The synovium of four groups of rabbits were scraped off their joints to conduct in vitro culture of SMSCs,as well as the morphological observation and identification of SMSCs.The venous bloods of rabbits were extracted to prepare PRP by centrifugation.The contents of PRP,platelet and growth factor in blood were compared.The SMSCs and PRP were injected into the knee joint cavity of three groups of rabbits with model.After 2,4 and 6 weeks of injection treatment,the repair statuses of cartilages at defection area of different groups were evaluated according to cartilage repair scoring table of International Association for Cartilage Repair(ICRS).Results:The primary synovial cells of rabbit knee joint synovium were initially round in shape after isolation,but almost all of them were spindle shaped after passage.The positive detection rates of SMSCs surface antigen CD73,CD90 and CD105 of 4 group were respectively 100%,99.22%and 99.99%.The CD45 detection was 0.5%,which indicated that they possessed the property of stem cell.The platelet count of 4 groups showed that the platelet concentration in PRP was approximate 6 times of that in whole blood.The concentrations of platelet derived growth factor(PDGF),transforming growth factor-β(TGF-β)and vascular endothelial growth factor(VEGF)were respectively(569.15±57.48)ng/mL,(633.56±63.90)ng/mL and(1 243.55±106.04)ng/mL in PRP,which were approximately 5 times,6 times and 7 times of that in whole blood,respectively.After 2 weeks of injection treatment for joint cavity,there was no significant statistical difference in the scores of cartilage repair among 4 groups(P>0.05).At 4 and 6 weeks of injection treatment,the morphological and histological score of cartilage repair of the SMSCs+PRP group were significantly higher than those of the blank group,and the differences were significant(t4 week=6.35,9.15,t6 week=8.16,8.60,P<0.05),respectively.Conclusion:The repair effect of SMSCs combined with PRP on cartilage injury of rabbit is significantly better than that of single PRP and single SMSCs,respectively,and all of them are better than those without treatment.SMSCs combined with PRP can significantly improve the effect of self-repair of cartilage injury.

In vitro construction of cartilage organoids based on extracellular matrix microcarriers of cartilage / 中华创伤杂志

Objective:To study the in vitro construction of functional and self-renewing cartilage organoids based on cartilage acellular extracellular matrix (ECM) microcarriers.Methods:Fresh porcine articular cartilage was taken. The merely crushed cartilage particles were set as natural cartilage group and ECM microcarriers of appropriate particle size, which were prepared by the acellular method of combining physical centrifugation and chemical extraction, were set as microcarrier group. Cartilage organoids were constructed by loading human umbilical cord mesenchymal stem cells (hUCMSCs) and human chondrocytes (hCho) with a ratio of 3∶1 with microcarriers through a rotating bioreactor. The organoids with different induction times were divided into 0-, 7-, 14-, and 21-day induction groups. The cell residues of the microcarrier group and natural cartilage group were evaluated by 4′, 6-diaminidine 2-phenylindole (DAPI) fluorescence staining and DNA quantitative analysis. The retention of microcarrier components was observed by Safranin O and toluidine blue stainnings, and the collagen and glycosaminoglycan (GAGs) levels in the microcarrier group and the natural cartilage group were determined by colorimetric method and dimethyl-methylene blue (DMMB) method. The microcarriers were further characterized by scanning electron microscopy and energy dispersive spectroscopy. The hUCMSCs cultured with Dulbecco′s Modified Eagle′s Medium (DMEM) supplemented with fetal bovine serum (FBS) in a volume fraction of 10% was used as the control group and the hUCMSCs cultured with the microcarrier extract was used as the experimental group. Subgroups of hUCMSCs cultured at 3 time points: 1, 3 and 5 days were set up in the two groups separately. Cell Counting Kit 8 (CCK-8) was used to detect the biocompatibility of the two groups. The cellular activity of the organoids of the 0-, 7-, 14-, and 21-day induction groups was detected by live/dead staining and the self-renewal ability of the cartilage organoids of the 14-day induced group was identified by Ki67 fluorescence staining. The organoids of the 7-, 14-, and 21-day induction groups were detected by RT-PCR in terms of the expression levels of chondrogenesis-related marker aggrecan (ACAN), type II collagen (COL2A1), SRY-related high mobility group-box gene-9 (SOX9), cartilage hypertrophy-and mineralization-related marker type I collagen (COL1A1), Runt-related transcription factor-2 (RUNX2), and osteocalcin (OCN). Colorimetric and DMMB assays were performed to determine the ability of organoids in the 0-, 7-, 14-, and 21-day induction groups to secrete collagen and GAGs.Results:The results of DAPI fluorescent staining showed that the natural cartilage group had a large number of nuclei while the microcarrier group hardly had any nuclei. The DNA content of the microcarrier group was (7.8±1.8)ng/mg, which was significantly lower than that of the natural cartilage group [(526.7±14.7)ng/mg] ( P<0.01). Saffranin O and toluidine blue staining showed that the microcarrier was dark- and uniform-colored and it kept a lot of cartilage ECM components. The collagen and GAGs contents of the microcarrier group were (252.9±1.4)μg/mg and (173.4±0.8)μg/mg, which were significantly lower than those of the natural cartilage group [(311.9±2.2)μg/mg and (241.3±0.7)μg/mg] ( P<0.01). Scanning electron microscopy showed that the surface of the microcarriers had uneven and interleaved collagen fiber network. The results of energy spectrum analysis showed that elements C, O and N were evenly distributed in the microcarriers, indicating that the composition of the microcarrier was uniform. The microcarrier had good biocompatibility and there was no statistical significance in the results of CCK-8 test between the control group and the experimental group after 1 and 3 days of culture ( P>0.05). After 5 days of culture, the A value of the experimental group was 0.53±0.02, which was better than that of the control group (0.44±0.03) ( P<0.05). In the 0-, 7-, 14-, and 21-day induction groups, hUCMSCs and hCho were attached to the surface of the microcarriers, with good cellular activity, and the live/death rates were (70.6±1.1)%, (80.5±0.6)%, (94.5±0.9)%, and (90.8±0.5)% respectively ( P<0.01). There were a large number of Ki67 positive cells in cartilage organoids. RT-PCR showed that the expression levels of ACAN, COL2A1, SOX9, COL1A1, RUNX2 and OCN were 1.00±0.09, 1.00±0.24, 1.00±0.18, 1.00±0.03, 1.00±0.06 and 1.00±0.13 respectively in the 7-day induction group; 4.16±0.28, 5.09±1.25, 5.65±1.05, 0.47±0.01, 1.68±0.02 and 0.21±0.06 respectively in the 14-day induction group; 13.42±0.92, 3.07±0.21, 1.84±1.08, 2.72±0.17, 2.91±0.18 and 3.32±1.20 respectively in the 21-day induction group. Compared with the 7-day induction group, the expression levels of ACAN, COL2A1, SOX9 and RUNX2 in the 14-day group were increased ( P<0.05), but COL1A1 expression level was decreased ( P<0.05), with no significant difference in OCN expression level ( P>0.05). Compared with the 7-day induction group, the expression levels of ACAN, COL1A1 and RUNX2 in the 21-day induction group were significantly increased ( P<0.01), with no significant differences in the expression levels of COL2A1, SOX9 and OCN ( P>0.05). Compared with the 14-day induction group, the expression levels of ACAN, COL1A1, RUNX2 and OCN in the 21-day group were increased ( P<0.05 or 0.01), with no significant difference in the expression level of COL2A1 ( P>0.05), but the expression level of SOX9 was decreased ( P<0.05). The contents of collagen in 0-, 7-, 14-and 21-day induction groups were (219.15±0.48)μg/mg, (264.07±1.58)μg/mg, (270.83±0.84)μg/mg and (280.01±0.48)μg/mg respectively. The GAGs contents were (171.18±1.09)μg/mg, (184.06±1.37)μg/mg, (241.08±0.84)μg/mg and (201.14±0.17)μg/mg respectively. Compared with the 0-day induction group, the contents of collagen and GAGs in 7-, 14-, and 21-day induction groups were significantly increased ( P<0.01), among which the content of collagen was the lowest in 7-day induction group ( P<0.01) but the highest in the 21-day induced group ( P<0.01); the content of GAGs was the lowest in the 7-day induced group ( P<0.01) but the highest in the 14-day induction group ( P<0.01). Conclusions:The microcarriers prepared by combining physical and chemical methods are decellularized successfully, with more matrix retention, uniform composition and on cytotoxicity. By loading microcarriers with hUCMSCs and hCho, cartilage organoids are successfully constructed in vitro, which are characterized by good cell activity, self-renewal ability, strong expression of genes related to chondrogenesis and secretion of collagen and GAGs. The cartilage organoids constructed at 14 days of induction have the best chondrogenic activity.

Adjustable external fixation traction combined with arthroscopic microfracture for treatment of osteochondral lesions of the talus / 中华创伤骨科杂志

Objective:To investigate the clinical effects of adjustable external fixation traction combined with arthroscopic microfracture in the treatment of osteochondral lesions of the talus (OLT).Methods:A retrospective study was conducted to analyze the data of 27 OLT patients who had been treated at Department of Orthopedics, Beijing Rehabilitation Hospital from May 2017 to March 2022. There were 16 males and 11 females, aged (32.4±7.2) years. Lesion site: 23 medial and 4 lateral cases; Hepple staging: 7 cases at stage Ⅰ, 15 cases at stage Ⅱ, and 5 cases at stage Ⅲ; disease duration: (10.6±3.3) months. All the patients were treated by adjustable external fixation traction combined with arthroscopic microfracture. Recorded were the patients' visual analogue scale (VAS) pain scores and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at 6 months and 12 months after surgery, levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor- α (TNF- α) at 1 month after surgery, lesion area at 12 months after surgery, and incidence of complications. Results:The follow-up time for this cohort was (16.2±6.7) months. The AOFAS score was (61.52±6.75) points before surgery, (84.15±5.56) points at 6 months after surgery and (95.67±4.30) points at 12 months after surgery. The VAS score was (5.88±1.02) points before surgery, (2.12±0.48) points at 6 months after surgery and (0.66±0.36) points at 12 months after surgery. The two-by-two comparisons between the 3 time points for the above items were statistically significant ( P<0.05). IL-1 was (32.37±6.64) pg/mL, IL-6 (34.04±7.12) pg/mL, and TNF- α (17.89±4.96) ng/L at 1 month after surgery in the 27 patients, all of which were significantly lower than their preoperative levels [(96.63±14.80) pg/mL, (102.33±20.42) pg/mL, and (54.48±9.33) ng/L] ( P<0.05). The lesion area was (28.66±6.52) mm 2 at 12 months after surgery, significantly smaller than the value before surgery [(128.52±11.32) mm 2] ( P<0.05). Infection at the adjustable external fixation needle track occurred in 1 patient and lower limb thrombosis in 2 patients. Conclusion:In the treatment of OLT, adjustable external fixation and traction combined with arthroscopic microfracture can achieve satisfactory results and improve symptoms for the patients.

Effects of marathon exercise on knee cartilage volume and T2 relaxation time / 中华骨科杂志

Objective:To investigate the effects of marathon exercise on knee cartilage volume and T2 relaxation time (T2 value) based on MRI.Methods:From December 2018 to December 2021, 25 healthy volunteers without long-distance running habits and 32 non-professional marathon runners with long-term long-distance running were recruited to undergo knee MRI 3D water-selective excitation (three dimensional water-selective excitation, 3D-WATS) and T2 mapping imaging were performed, and the cartilage volumes in 5 knee areas and T2 values in 42 subareas were extracted for analysis. To compare the cartilage volume and its ratio to body surface area of knee joint of healthy volunteers and non-professional marathon runners, the T2 value of cartilage in each subregion, and the correlation between marathon exercise intensity and the volume and T2 value of cartilage in different regions.Results:Compared with healthy volunteers, there was no significant difference in cartilage volume or the ratio of body surface area to body volume of non-professional marathon runners ( P>0.05). There were significant differences between healthy volunteers and non-professional marathon runners in cartilage T2 values of the median layer of medial condyle of femur (47.61±5.65 ms and 44.29±6.10 ms) and the deep layer of medial condyle of femur (36.82±9.05 ms and 31.67±7.59 ms), deep precondylar area of medial femur (38.37±4.68 ms and 34.09±4.19 ms), shallow area of medial condylar area of femur (52.17±11.11 ms and 45.51±7.76 ms), middle layer of medial condylar area of femur (49.09±5.08 ms and 45.63±5.04 ms), medial layer of anterior condylar region of lateral femur (45.69±4.68 ms and 42.57±5.77 ms), superficial layer of posterior condylar region of lateral femur (55.42±18.41 ms and 47.99±8.39 ms), deep layer of anterior tibial medial plateau (33.40±7.76 ms and 29.03±5.69 ms), deep layer of posterior tibial medial plateau (31.28±5.02 ms and 27.92±5.99 ms), deep layer of patellofemoral surface (35.65±6.99 ms and 32.30±5.28 ms), respectively ( P<0.05). In non-professional marathon runners, the medial tibial plateau cartilage volume was negatively correlated with step frequency ( r=-0.371, P=0.035), the lateral femoral condylar cartilage volume was negatively correlated with step frequency ( r=-0.365, P=0.043), and the lateral tibial plateau cartilage volume was negatively correlated with step frequency ( r=-0.550, P=0.001). The T2 value of the medial layer cartilage in the anterior tibial medial plateau region was negatively correlated with body weight ( r=-0.277, P=0.039) and body mass index ( r=-0.290, P=0.030). The T2 value of the superficial layer of patellofemoral surface was negatively correlated with the amount of running in 3 months ( r=-0.457, P=0.010). The superficial T2 value in the posterior lateral plateau of the tibia was negatively correlated with stride length ( r=-0.437, P=0.014), and the medial layer cartilage T2 value in the anterior condylar area of the lateral femur was negatively correlated with stride frequency ( r=-0.380, P=0.035). Conclusion:Marathon exercise had little effect on the knee cartilage volume, but had a certain effect on the cartilage T2 value, resulting in changes in cartilage structure. The higher the step frequency, the smaller the cartilage volume. The greater the body weight or body mass index, the greater the amount of running in 3 months, and the greater the stride length, the lower the cartilage T2 value.

Advances in Pharmacological Research on Anti-knee Osteoarthritis of Active Components of Salviae Miltiorrhizae Radix et Rhizoma / 中药新药与临床药理

Knee osteoarthritis(KOA)is a degenerative joint disease with a high incidence,which has seriously affected the quality of life of middle-aged and elderly people.Salviae Miltiorrhizae Radix et Rhizoma,a commonly used traditional Chinese medicinal for activating blood and removing stasis,has been proved to have a certain preventive effect on KOA in basic research and clinical application.Studies have found that the active ingredients of Salviae Miltiorrhizae Radix et Rhizoma have a variety of anti-KOA effects,such as regulation of inflammatory factors,anti-oxidative stress,inhibition of chondrocyte apoptosis,regulation of cartilage matrix degradation,and promotion of chondrocyte autophagy.It can reduce joint pain and inflammatory edema,delay articular cartilage degeneration,and maintain cartilage matrix homeostasis.This paper reviews the effect and mechanism of the effective components from Salviae Miltiorrhizae Radix et Rhizoma on the prevention and treatment of KOA,and analyzes the shortcomings of its related research.Our aim is to provide reference for the clinical treatment of KOA.

Effect of Danggui Niantongtang on Intestinal Flora of Knee Osteoarthritis Mice Based on 16S rDNA Sequencing / 中国实验方剂学杂志

ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg-1）， medium-dose Danggui Niantongtang group （1.638 g·kg-1）， high-dose Danggui Niantongtang group （3.276 g·kg-1）， and Meloxicam group （0.975 mg·kg-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.

Mechanism of Xibining Ⅱ Combined with ADSC-Exos in Improving Knee Osteoarthritis by Regulating Mitochondrial Autophagy / 中国实验方剂学杂志

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.

Repairment effect of intra-articular adipose stem cell injection on articular cartilage destruction in rabbit model with temporomandibular joint osteoarthritis and its mechanism / 吉林大学学报(医学版)

Objective:To discuss the repairment effect of intra-articular injection of adipose derived stem cells(ADSCs)on articular cartilage destruction in the temporomandibular joint osteoarthritis(TMJOA)model rabbits,and to clarify the possible mechanism.Methods:Twenty-seven rabbits were randomly divided into control group,model group,and ADSCs group.The ADSCs of the rabbits were extracted and cultured.The rabbit TMJOA model was prepared by monosodium-iodoacetate(MIA)injection technique.The temporomandibular joint cavity of the TMJOA model rabbits in ADSCs group was given two continuous intra-articular injections of 1.0×106 mL-1 ADSCs,while the rabbits in control and model group were given sequivalent volume of saline into the temporomandibular joint cavity.After 8 weeks,Micro-CT scan was performed on the temporomandibular joints of the rabbits in various groups;the bone volume fraction(BV/TV),bone surface area/bone volume(BS/BV),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular number(Tb.N)of condyles tissue of the rabbits in various groups were analyzed;HE staining was used to observe the pathomorphology of condyles tissue of the rabbits in various groups;immunohistochemistry was used to detect the localization and expression levels of SRY-related high mobility group box gene 9(SOX9),matrix metalloproteinase-13(MMP-13),and vascular endothelial growth factor(VEGF)proteins in condyles tissue of the rabbits in various groups;Western blotting method was used to detect the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in various groups.Results:The micro-CT scan results showed that compared with control group,the BV/TV,Tb.Th,and Tb.N of condyles tissue of the rabbits in model group were significantly decreased(P<0.05),while the BS/BV and Tb.Sp were significantly increased(P<0.05);compared with model group,the BV/TV,Tb.Th,and Tb.N in condyles tissue of the rabbits in ADSCs group were significantly increased(P<0.05),and the BS/BV and Tb.Sp were significantly decreased(P<0.05).The HE staining results showed that the condylar cartilage surface of the rabbits in control group was smooth with clear layers and intact structure;compared with control group,the surface of condyles tissue of the rabbits in model group was irregular with thickened hypertrophic layer and areas of cell depletion and clustering;compared with model group,the pathological damage of condyles tissue of the rabbits in ADSCs group was significantly decreased.The immunohistochemical staining results showed that compared with control group and ADSCs group,the number of brown granule in condyles tissue of the rabbits in model group was increased,mainly concentrated in the hypertrophic layer,especially in the bone cartilage junction site and the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the number of brown granule in condyles tissue of the rabbits in ADSCs group was significantly decreased,and the expression levels of SOX9,MMP-13,and VEGF proteins were significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in ADSCs group were significantly decreased(P<0.05).Conclusion:Intra-articular injection of ADSCs can effectively repair the cartilage destruction in TMJOA,alleviate the cartilage injury,and mitigate the progression of osteoarthritis.

Construction and application of an injectable cartilage graft / 实用口腔医学杂志

Objective:To explore a set of procedures for the effictive granulation of cartilage,and to construct injectable cartilage graft with platelet-rich gel(PRG),and to evaluate its effects in nude mice models.Methods:The costal cartilage of adult male rab-bits was cut into pieces and placed in a mortar for 30-60 s freezing in liquid nitrogen and grinding for a short time to obtain granular cartilage.Blood was collected from the middle ear artery and PRG was prepared by double centrifugation.Granular cartilage and the mixture of granular cartilage and PRG were injected subcutaneously in nude mice of control group(n=5)and experimental group(n=5)respectively.8 weeks after injection,the gross morphology observation and histological examination were pertormed.The nasal dor-sum augmentation model of nude mice was established in the experimental group.Results:The cartilage particles were in the size of 10-500 pm in diameter after frozen grinding,and injection could be realized.In vitro culture showed that the cell survival rate of granular cartilage reached to 80％.In vivo test showed that the sample morphology of the control group was insignificant,and the sur-face was grainy.That of the experimental group was well maintained,and the surface was smooth with obvious capillaries.The sam-ples of experimental group achieved significant augmentation in the nude mouse model of nasal dorsum augmentation.Conclusion:Freeze-milling technology can achieve efficient granulation of cartilage,and the graft constructed with PRG gel is suitable for maxillo-facial cartilage transplantation repair.

Preparation and in vitro evaluation of a three-dimensional porous cartilage scaffold made of silk fibroin/gelatin/chitosan / 中国组织工程研究

BACKGROUND:Cartilage defects are one of the major clinical challenges faced by orthopedic surgeons.Tissue engineering is an interdisciplinary approach that combines knowledge of engineering and cell biology to provide new ideas and approaches for the repair of cartilage defects. OBJECTIVE:To prepare a multi-component composite scaffold based on silk fibroin,gelatin,and chitosan to screen for a three-dimensional porous scaffold suitable for cartilage regeneration by evaluating its physicochemical properties and biological performance. METHODS:Four groups of porous scaffolds were prepared by vacuum freeze-drying method using silk fibroin,gelatin and chitosan as the base materials,namely chitosan/gelatin scaffold,silk fibroin/chitosan scaffold,silk fibroin/gelatin scaffold and silk fibroin/chitosan/gelatin scaffold.The suitable cartilage scaffolds were screened by scanning electron microscopy,X-ray diffractometer,porosity,water absorption and swelling rate,biodegradation rate and mechanical property detection.Then cartilage scaffolds were co-cultured with chondrocytes isolated and extracted from patients with osteoarthritis.The feasibility of porous scaffolds for cartilage injury repair was evaluated in vitro by cell adhesion rate assay,cell live-dead staining and cell activity proliferation assay. RESULTS AND CONCLUSION:(1)All four groups of scaffolds had porous structures.The comprehensive physical performance test results showed that the silk fibroin/gelatin/chitosan scaffold was more in line with the requirements of cartilage defect repair.This scaffold had a pore size of(176.00±53.68)μm,the porosity of(80.15±2.57)%,and water absorption and swelling rate of(3 712±358)%.After immersion in PBS containing lysozyme for 28 days in vitro,the biodegradation rate was(46.87±3.25)%,and it had good mechanical properties.(2)Chondrocytes could adhere well on the silk fibroin/gelatin/chitosan scaffold,and the cell adhesion rate increased with time.CCK8 and live/dead cell double staining results showed that silk fibroin/gelatin/chitosan scaffold had good biocompatibility and low cytotoxicity.(3)The results showed that silk fibroin/gelatin/chitosan scaffold had a highly hydrated 3D structure,suitable pore size and porosity,good biodegradability and superior mechanical properties,which can provide a good reticular skeleton and microenvironment for nutrient transport and chondrocyte attachment and proliferation.

Cartilage targeting function in the drug delivery system by intra-articular injection for the treatment of osteoarthritis / 中国组织工程研究

BACKGROUND:Intra-articular injection played an important role in the treatment of osteoarthritis and has more options with the development of novel drug delivery systems.The cartilage targeting function is aimed at the adhesion or retention of drugs in the cartilage layer to form a drug bank to achieve slow release and precise drug delivery. OBJECTIVE:To review various cartilage targeting biomaterials and their characteristics in the treatment of osteoarthritis by articular injection. METHODS:Using the term"osteoarthritis,drug carrier,drug delivery,cartilage targeting,penetrate"as key words,relevant articles were searched in CNKI,WanFang and PubMed databases.According to inclusion and exclusion criteria,67 articles were finally selected for further review. RESULTS AND CONCLUSION:The research on cartilage-targeting biomaterials is mainly divided into two directions.One is the combination of electrostatic interaction,such as the combination of positively charged biomaterials and negatively charged polysaccharides in cartilage.This kind of scheme is operable and easy to modify,but limited by the shortcomings of electrostatic interaction itself,it performs badly in advanced osteoarthritis.Another one is the specific binding of various components in cartilage which is strong and reliable,and related biomaterials have excellent performance in advanced osteoarthritis,which is an important direction for future cartilage-targeted therapy.

Application of core-shell structured nanofibers in oral tissue regeneration / 中国组织工程研究

BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.

Research status and application prospect of cytokine therapy for osteoarthritis / 中国组织工程研究

BACKGROUND:In cartilage degeneration in osteoarthritis,cytokines and signaling pathways that target chondrocytes play an important role. OBJECTIVE:To review the latest research progress of osteoarthritis related cytokines and signaling pathways in recent years,such as the mechanism of action and treatment modalities,in order to provide a basis for future exploration of new therapeutic targets and modalities. METHODS:Literature search was conducted on CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases.Chinese search terms were"osteoarthritis,cytokines,signal pathway,chondrocyte,inflammation,treatment".Finally,60 papers were included for review. RESULTS AND CONCLUSION:(1)In current studies,it is believed that the specific mechanism of osteoarthritis is not clear,and a large number of studies have shown that osteoarthritis is strongly associated with cytokines and signaling pathways,which is a complex process of action.Relevant studies taking cytokines and signaling pathways as therapeutic breakthroughs are also the current hot spot.(2)The receptor antagonists of pro-inflammatory factors such as interleukin 1 are not effective in the treatment of osteoarthritis,and more studies turn to gene therapy.(3)The therapeutic methods of transforming growth factor β,recombinant factors of Wnt signaling pathway,gene therapy and mesenchymal stem cells have obtained positive research results.However,basic and clinical studies on safety and efficacy are likely to be conducted in future studies.(4)At present,relevant therapeutic methods such as platelet-rich plasma have been widely used in clinical practice,while recombinant factor,gene therapy and mesenchymal stem cell therapy are all in the research stage,among which mesenchymal stem cell therapy and gene therapy are expected to make breakthroughs in the field of cartilage repair and regeneration,and are worthy of expectation in the future.However,more clinical and basic studies are needed to verify its effectiveness and safety,explore its mechanism of action and scope of application,and set standards for its clinical use.

Effect of electroacupuncture on the expression of P53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis / 中国组织工程研究

BACKGROUND:There are many treatment methods for knee osteoarthritis,among which electroacupuncture,as an important non-drug treatment,is effective in the treatment of knee osteoarthritis,but its exact mechanism is not clear. OBJECTIVE:Effect of electroacupuncture on the expression of p53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis. METHODS:Eight 6-month-old male Sprague-Dawley rats were included in the young group and sixteen 24-month-old male Sprague-Dawley rats were randomly divided into old group(n=8)and electroacupuncture group(n=8).The rats in the electroacupuncture group received electroacupuncture stimulation once a day,5 days a week,for 8 continuous weeks,and the other two groups did not do any treatment.Eight weeks later,the level of type Ⅱ collagen C-terminal peptide in peripheral blood was detected by ELISA,the morphology of left knee cartilage and subchondral bone was observed by safranin O-fast green staining,the degree of knee cartilage degeneration was evaluated by modified Mankin's score,the microstructure of left knee cartilage and subchondral bone was detected by micro-CT,and the expression levels of matrix metalloproteinase 13,P53,P21 Mrna and protein were detected by RT-PCR and western blot respectively. RESULTS AND CONCLUSION:Compared with the young group,the level of C-terminal peptide of type Ⅱ collagen in the peripheral blood was increased in the old group(P<0.05).The micro-CT results showed that the bone volume fraction,bone mineral density and the number of bone trabeculae were decreased in the old group compared with the young group(P<0.05),while the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that in the old group,the surface layer of cartilage was uneven with fissures,the morphology of chondrocytes was irregular and stained unevenly,the boundary between the cartilage and subchondral bone was blurred,and the matrix loss was serious.The Mankin's score was higher in the old group than the young group(P<0.05).The expression of matrix metalloproteinase 13,P53,P21 at Mrna and protein levels increased in the old group compared with the young group(P<0.05).Compared with the old group,electroacupuncture decreased the level of C-terminal peptide of type Ⅱ collagen(P<0.05),increased the bone volume fraction,bone mineral density and the number of bone trabeculae(P<0.05),and decreased the trabecular separation(P<0.05).Safranin O-fast green staining showed that in the electroacupuncture group,the surface of cartilage was smooth and red staining was uniform,and the cell morphology and structure were between the young group and the old group.Following electroacupuncture treatment,the Mankin's score(P<0.05),matrix metalloproteinase 13 and P21 Mrna expression(P<0.05),and matrix metalloproteinase 13 and P53 protein expression decreased(P<0.05),while there was a decreasing trend of P53 Mrna and P21 protein expression,but with no statistical significance(P>0.05).To conclude,electroacupuncture may delay articular cartilage degeneration and subchondral osteoporosis in aged rats by inhibiting the expression of P53 and P21,so as to protect joints and delay joint aging.

Mechanism of Mongolian Medicine Erden-uril on osteoarthritis in rats / 中国组织工程研究

BACKGROUND:The clinical application of Mongolian Medicine Erdun-uril in the treatment of osteoarthritis is effective,but its therapeutic effect and related mechanism are still unclear. OBJECTIVE:To observe the repairing process of osteoarthritis in rats by Mongolian Medicine Erdun-uril and analyze its mechanism. METHODS:Thirty male Sprague-Dawley rats(8 weeks of age)were selected to establsih an osteoarthritis model using intraarticular injection of sodium iodoacetate solution into the unilateral knee joint.Two weeks after modeling,the model rats were randomly divided into three groups:control group(n=6)was given normal saline by gavage,and low and high dose groups(n=12 per group)were given Erdun-uril 1.4 and 2 g,respectively,3 times per day.After 2 and 4 weeks of continuous administration,blood samples,articular cartilage and periarticular bone tissue were taken from rats to detect changes in cartilage metabolic markers(cartilage oligomeric matrix protein,proteoglycan),bone metabolic markers(bone alkaline phosphatase,keratan sulfate),inflammatory markers(interleukin 6,tumor necrosis factor α),lipid metabolic markers(total cholesterol,triacylglycerol).Histopathological changes were also observed. RESULTS AND CONCLUSION:qRT-PCR results showed that after 2 and 4 weeks of administration,the mRNA expression of cartilage oligomeric matrix protein,proteoglycan and bone alkaline phosphatase and keratan sulfate in knee cartilage of rats were significantly reduced in the low and high dose groups compared with the control group(P<0.05,P<0.01,P<0.001),with the reduction being more significant in the high dose group.After 2 and 4 weeks of administration,compared with the control group,serum tumor necrosis factor α and interleukin 6 levels were decreased(P<0.01,P<0.001)and total cholesterol and triacylglycerol levels were increased(P<0.05,P<0.01,P<0.001)in the low and high dose groups,with the improvement being more significant in the high dose group.Hematoxylin-eosin staining results showed that in the control group,there were large defective areas on the surface of the knee cartilage with unknown structure and severe inflammatory cell infiltration;in the low dose group,the surface of the knee cartilage was rough with disordered cell arrangement and the cartilage structure did not improve significantly after 2 weeks of administration,while the number of inflammatory cells in the knee cartilage was reduced and the cartilage structure was restored to some extent after 4 weeks of administration;in the high dose group,the structure of the knee cartilage become clear after 2 weeks of administration and even clearer after 4 weeks of administration,and the inflammation was significantly reduced after 2 weeks of administration.To conclude,Mongolian Medicine Erdun-uril with better anti-inflammatory properties can improve cartilage metabolism and obviously alleviate osteoarthritis in rats.

Three-dimensional finite element analysis of effects of partial anterior cruciate ligament rupture on knee joint stress / 中国组织工程研究

BACKGROUND:Anterior cruciate ligament injury tends to lead to secondary meniscus injury and osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by anterior cruciate ligament injury. OBJECTIVE:To study the effect of partial rupture of the anterior cruciate ligament on the stress of medial and lateral meniscus and articular cartilage of knee joint by finite element analysis. METHODS:The CT and MRI images of the knee joint of a healthy volunteer were selected,and the scan data were imported into Mimics,Geomagic and SolidWorks software.After registration and fusion,four kinds of three-dimensional knee joint models were established:models of intact anterior cruciate ligament,rupture of the posterior external tract of anterior cruciate ligament,rupture of the anterior internal tract of anterior cruciate ligament,and absence of anterior cruciate ligament.Finally,data were imported into Ansys software to apply four different modes of loads to the knee joint:Longitudinal loads of 750 N were applied to the top of the femur;longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia;a longitudinal load of 750 N and a varus moment of 10 Nm were applied to the top of the femur to simulate genu varus;750 N longitudinal load and 4 Nm internal rotation moment were applied to the proximal end of the femur to simulate knee internal rotation.The finite element analysis of biomechanical stress changes of the meniscus and articular cartilage of the knee joint was carried out. RESULTS AND CONCLUSION:(1)In the straight position of the knee joint,when the anterior medial tract of the anterior cruciate ligament was broken and the anterior cruciate ligament was missing under longitudinal loads of 750 N at the top of the femur,the total stress and peak value of meniscus increased significantly,but the stress distribution of the meniscus and the stress of articular cartilage did not change significantly.In longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia,the fracture of the anterior internal tract of the anterior cruciate ligament increased the tibia forward,the compressive stress of posterior angle of the meniscus increased,and the stress of the articular cartilage did not change significantly.During simulating genu varus,the posterior angular stress of the lateral meniscus decreased,the stress of the medial meniscus increased,and the stress of articular cartilage slightly decreased when anterior cruciate ligament injuries were complete.When the anterior internal tract of the anterior cruciate ligament was broken or absent under knee internal rotation,the equivalent stress peak value of femoral cartilage and tibia cartilage shifted from medial cartilage to lateral cartilage,and the stress peak value of meniscus increased significantly.At this time,the anterior internal tract of the anterior cruciate ligament played a leading role in the rotational stability of the knee joint.(2)These results indicate that the risk of secondary meniscus injury in patients with anterior and medial anterior cruciate ligament band rupture was much higher than that in patients with posterior and external anterior cruciate ligament band rupture when the knee was in the upright standing position,varus and pronation,and there was no significant difference in the impact on articular cartilage.