Treatment of Chondral Lesions in the Knee / Tratamento das lesões condrais no joelho

Abstract Articular cartilage injuries are common and lead to early joint deterioration and osteoarthritis. Articular cartilage repair techniques aim at forming a cartilaginous neo-tissue to support the articular load and prevent progressive degeneration. Several techniques are available for this purpose, such as microfracture and chondrocyte transplantation. However, the procedural outcome is often fibrocartilage, which does not have the same mechanical resistance as cartilaginous tissue. Procedures with autologous osteochondral graft have a morbidity risk, and tissue availability limits their use. As such, larger lesions undergo osteochondral transplantation using fresh or frozen grafts. New techniques using minced or particulate cartilage fragments or mesenchymal stem cells are promising. This paper aims to update the procedures for treating chondral lesions of the knee.

Resumo As lesões da cartilagem articular são comuns e levam à deterioração precoce da articulação e ao desenvolvimento da osteoartrite. As técnicas de reparo da cartilagem articular visam a formação de um neo-tecido cartilaginoso capaz de suportar carga articular e evitar a progressão da degeneração. Há várias técnicas disponíveis para esse fim, como a microfratura e o transplante de condrócitos. Entretanto muitas vezes o desfecho do procedimento é a formação de fibrocartilagem, que não possui a mesma resistência mecânica do tecido cartilaginoso. Em outros procedimentos, nos quais é realizado enxerto osteocondral autólogo, há risco de morbidade associada ao procedimento, além da disponibilidade limitada de tecido. Por esse motivo, o transplante osteocondral, utilizando enxertos a fresco ou congelados tem sido utilizado para lesões de maior volume. Por fim, novas técnicas utilizando fragmentos de cartilagem picada ou particulada, assim como o uso de células tronco mesenquimais se apresentam como promissores. O objetivo desse artigo é realizar uma atualização dos procedimentos para tratamento das lesões condrais do joelho.

Refixation of the Excised Acetabular Labrum can Affect the Structural Changes of Cartilage Surface in the Hip Joint / La Refijación del Labrum Acetabular Extirpado Puede Afectar los Cambios Estructurales de la Superficie del Cartílago en la Articulación Coxal

SUMMARY: Refixation of the damaged acetabular labrum is a method of surgical treatment of the hip joint that can promote the repair of joint function after injury and prevent premature osteoarthritis. We sought to determine the condition of the hip joint in rabbits 4 months after excision of the acetabular labrum and the condition of the joint after labral refixation. The articular cartilage of the femoral head and acetabulum was examined by histological methods, multipoint measurement of cartilage thickness, and the ratio between cartilage matrix and chondrocytes lacunae, and the condition of cartilage according to the OARSI grading scale was carried out. On this model, a correlation analysis was performed between the results of the OARSI grading scale and the data of linear morphometry. All these parameters made it possible to better assess changes in articular cartilage. The ratio between matrix and chondrocyte lacunae turned out to be a method that allows establishing early cartilage damage when erosion, fibrosis or deformation did not occur. We found significant differences between the condition of the cartilage after exicion of acetabular labrum and after labral refixation, which give hope to confirm that this surgical technique can delay or prevent progressive changes in the cartilage of the damaged hip joint.

La refijación del labrum acetabular dañado es un método de tratamiento quirúrgico de la articulación coxal, que puede promover la reparación de la función articular después de una lesión y prevenir la osteoartritis prematura. Intentamos determinar el estado de la articulación coxal en conejos de 4 meses después de la escisión del labrum acetabular y observar el estado de la articulación después de la refijación del labrum. El cartílago articular de la cabeza femoral y el acetábulo se examinó por métodos histológicos, se midió a través de multipunto el grosor del cartílago y se realizó la relación entre la matriz del cartílago y las lagunas de condrocitos, y se llevó a cabo la condición del cartílago según la escala de clasificación OARSI. Sobre este modelo se realizó un análisis de correlación entre los resultados de la escala de calificación OARSI y los datos de la morfometría lineal. Todos estos parámetros permitieron evaluar mejor los cambios en el cartílago articular. La relación entre la matriz y las lagunas de condrocitos resultó ser un método que permite establecer temprano el daño del cartílago cuando no se presentó erosión, fibrosis o deformación. Encontramos diferencias significativas entre la condición del cartílago después de la extirpación del labrum acetabular y después de la refijación del labrum, lo que da la esperanza de confirmar que esta técnica quirúrgica puede retrasar o prevenir cambios progresivos en el cartílago de la articulación coxal dañada.

Electroacupuncture improves motor function of rats with osteoarthritis by alleviating joint inflammation through the Wnt-7B/β-catenin signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of electroacupuncture on osteoarthritis in rats and explore the possible mechanism.@*METHODS@#Thirty SD rats were randomly divided into osteoarthritis model group, electro-acupuncture group and control group (n=10), and in the former two groups, early osteoarthritis was induced using a modified DMM surgical modeling method. After successful modeling, the rats in the electro-acupuncture group were treated with electro-acupuncture at bilateral "Housanli" and "Anterior knee point". Behavioral tests of the rats were performed and scored using the LequesneMG scale. Subchondral bone degeneration was observed in each group, and serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP were measured using ELISA. The mRNA and protein expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7, and MMP-3 in the cartilage tissue of the knee joints were detected using RT-PCR and Western blotting.@*RESULTS@#In behavioral tests, the rats in the model and electroacupuncture groups had significantly higher LequesneMG scores after modeling than those in the control group (P < 0.05). After 20 days of treatment, LequesneMG scores were significantly lowered in rats in the electroacupuncture as compared with the model rats (P < 0.05). Imaging examination revealed obvious subchondral bone damage in both the electroacupuncture group and the model group, but the damages were significantly milder with former group. Compared with the model rats, the rats receiving electroacupuncture had significantly lower serum levels of IL-1β, ADAMTS-7, MMP-3 and COMP (P < 0.05) with also lower expressions of IL-1β, Wnt-7B, β-catenin, ADAMTS-7 and MMP-3 in the cartilage tissues at both the mRNA and protein levels (P < 0.05).@*CONCLUSION@#Electroacupuncture can alleviate joint pain and improve subchondral bone damage in rats with osteoarthritis by reducing IL-1β levels in the joint cartilage tissue and serum to alleviate joint inflammation and by reducing such cytokines as ADAMTS-7 and MMP-3 via regulating the Wnt-7B/β-catenin signaling pathway.

Systematic evaluation of the incidence of the knee donor area after autobone cartilage mosaic xentoplasty / 中国骨伤

OBJECTIVE@#To provide an overview of the incidence of knee donor -site morbidity after autologous osteochondral mosaicplasty.@*METHODS@#A comprehensive search was conducted in PubMed, EMbase, Wanfang Medical Network, and CNKI databases from January 2010 to April 20, 2021. Relevant literature was selected based on predefined inclusion and exclusion criteria, and data were evaluated and extracted. The correlation between the number and size of transplanted osteochondral columns and donor-site morbidity was analyzed.@*RESULTS@#A total of 13 literatures were included, comprising a total of 661 patients. Statistical analysis revealed an incidence of knee donor-site morbidity at 8.6% (57/661), with knee pain being the most common complaint, accounting for 4.2%(28/661). There was no significant correlation between the number of osteochondral columns and postoperative donor-site incidence (P=0.424, N=10), nor between the diameter size of osteochondral columns and postoperative donor-site incidence(P=0.699, N=7).@*CONCLUSION@#Autologous osteochondral mosaicplasty is associated with a considerable incidence of knee donor-site morbidity, with knee pain being the most frequent complaint. There is no apparent correlation between donor-site incidence and the number and size of transplanted osteochondral columns. Donors should be informed about the potential risks.

Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis / 中国修复重建外科杂志

OBJECTIVE@#To summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects.@*METHODS@#The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA.@*RESULTS@#Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA.@*CONCLUSION@#The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.

Relationship between trace elements in synovial fluid and cartilage and severity of knee osteoarthritis / 中国修复重建外科杂志

OBJECTIVE@#To investigate the relationship between trace elements in synovial fluid and cartilage and severity of knee osteoarthritis (KOA).@*METHODS@#Patients with KOA who underwent knee arthrocentesis or total knee arthroplasty (TKA) were recruited based on inclusion criteria between June 2021 and December 2021. Synovial fluid samples were obtained during knee arthrocentesis and TKA, and participants were divided into the mild group (grading Ⅰ/Ⅱ) and the severe group (grading Ⅲ/Ⅳ) according to the Kellgren-Lawrence grading (K-L grading). Cartilage samples with different degrees of wear were collected during the TKA from the same patient and were divided into mild wear (0-1 point) and severe wear (2-4 points) groups based on the Pelletier score. The contents of copper (Cu), zinc (Zn), and manganese (Mn) in synovial fluid and cartilage were evaluated by inductively coupled plasma mass spectrometry, and the differences between groups were compared.@*RESULTS@#A total of 33 synovial fluid samples were collected, including 19 specimens from 14 patients who underwent knee arthrocentesis of mild group, with 5 bilateral sides knee arthrocentesis in them, and 14 specimens from 14 TKA patients of severe group. The patients were significantly younger in the mild group than in the severe group ( P<0.05), but there was no significant difference in gender or body mass index between the two groups ( P>0.05). Nineteen pairs of cartilage samples with mild and severe wear were collected from severe KOA patients (K-L grading Ⅲ and Ⅳ), including 9 males and 10 females, with an average age of 70.4 years (range, 58-80 years). The body mass index ranged from 21.2 to 30.7 kg/m 2, with an average of 25.6 kg/m 2. The content of Zn in synovial fluid and cartilage from KOA patients was the highest, followed by Cu, and Mn was the lowest. The Cu content in synovial fluid was significantly higher in the severe group than in the mild group ( P<0.05), and in the severe wear group than in the mild wear group ( P<0.05). There was no significant difference in Zn and Mn content between the two groups ( P>0.05).@*CONCLUSION@#The Cu content increases with the severity of cartilage wear in patients with KOA.

Conceptos actuales en el diagnóstico y tratamiento de las lesiones del hueso subcondral / Current concepts in the diagnosis and treatment of subchondral bone injuries

La patología ósea subcondral incluye una amplia gama de patologías, como la artrosis, las fracturas por insuficiencia espontánea, la osteonecrosis y los traumatismos articulares. Todas muestran hallazgos típicos de imágenes de resonancia magnética (RM) denominados lesiones de la médula ósea (LMO). Sin embargo, la etiología y la evolución de las LMO en múltiples afecciones aún no están claras. Además, todavía no existe un protocolo de tratamiento estándar de oro para las LMO, es por esto que se están probando una variedad de modalidades de tratamiento con la esperanza de que puedan reducir el dolor y detener la progresión de la enfermedad. Nuestro propósito es presentar una revisión sobre los conceptos actuales para el diagnóstico y tratamiento de las LMO. Se realizó una revisión de la literatura que incluyó búsquedas en las bases de datos PubMed, Cochrane y Medline utilizando las siguientes palabras clave: lesiones de médula ósea subcondral, hueso subcondral, subcondroplastia, concentrado de médula ósea, plasma rico en plaquetas (PRP) y aumento óseo subcondral. Podemos concluir que el uso de nuevas técnicas biológicas para tratar las LMO, como el PRP y las células de la médula ósea, ha mostrado resultados clínicos prometedores. La investigación futura de las LMO será necesaria para abordar mejor las diferentes patologías y determinar las estrategias terapéuticas adecuadas. Todavía se necesitan estudios randomizados y controlados de alta calidad junto a revisiones sistemáticas para generar guías y recomendaciones para el tratamiento de las LMO.

Subchondral bone pathology includes a wide range of pathologies, such as osteoarthritis, spontaneous insufficiency fractures, osteonecrosis, and trauma. They show typical magnetic resonance imaging (MRI) findings termed bone marrow lesions (BMLs). However, the etiology and evolution of BMLs in multiple conditions remains unclear. There is still no gold standard treatment protocol in treating BML, and a variety of treatment modalities have been tested in the hope that they might reduce pain and stop disease progression.Our purpose was to write a current concepts review about diagnosis and treatment options for BMLs. A literature review was performed that included searches of PubMed, Cochrane, and Medline databases using the following keywords: Bone marrow lesions, subchondral bone, subchondroplasty, bone marrow concentrate, platelet-rich plasma (PRP), subchondral bone augmentation.The use of novel biologic techniques to treat BMLs, such as PRP and Bone Marrow Cells, has yielded promising clinical outcomes. Future research of BMLs will be mandatory to address the different pathologies better and determining appropriate treatment strategies. There is still a need for high-quality RCTs studies and systematic reviews in the future to enhance further treatment strategy in preventing or treating BMLs of the knee.

Impact of Hyaluronic Acid on the Viability of Mesenchymal Cells Derived from Adipose Tissue Grown in Collagen Type I/III Membrane / Impacto do ácido hialurônico na viabilidade das células mesenquimais derivadas do tecido adiposo cultivadas em membrana de colágeno tipo I/III

Abstract Objective To evaluate in vitro the viability of mesenchymal stem cells derived from adipose tissue (AD-MSCs) in different commercial solutions of hyaluronic acid (HA) before and after being sowed in collagen I/III membrane. Methods In the first stage, the interaction between AD-MSCs was analyzed with seven different commercial products of HA, phosphate buffered saline (PBS), and bovine fetal serum (BFS), performed by counting living and dead cells after 24, 48 and 72 hours. Five products with a higher number of living cells were selected and the interaction between HA with AD-MSCs and type I/III collagen membrane was evaluated by counting living and dead cells in the same time interval (24, 48 and 72 hours). Results In both situations analyzed (HA + AD-MSCs and HA + AD-MSCs + membrane), BFS presented the highest percentage of living cells after 24, 48 and 72 hours, a result higher than that of HA. Conclusion The association of HA with AD-MSCs, with or without membrane, showed no superiority in cell viability when compared with BFS.

Resumo Objetivo Avaliar in vitro a viabilidade das células-tronco mesenquimais derivadas do tecido adiposo (AD-CTMs) em diferentes soluções comerciais de ácido hialurônico (AH) antes e após serem semeadas em membrana de colágeno I/III. Métodos Na primeira etapa, analisou-se a interação entre AD-CTMs com sete diferentes produtos comerciais de AH, salina tamponada com fosfato (PBS, na sigla em inglês) e soro fetal bovino (SFB), realizada pela contagem das células vivas e mortas após 24, 48 e 72 horas. Foram selecionados cinco produtos com maior número de células vivas e avaliou-se a interação entre o AH com AD-CTMs e a membrana de colágeno tipo I/III pela contagem de células vivas e mortas no mesmo intervalo de tempo (24, 48 e 72 horas). Resultados Em ambas as situações analisadas (AH + AD-CTM e AH + AD-CTM + membrana), o SFB apresentou a maior porcentagem de células vivas após 24, 48 e 72 horas, resultado superior ao do AH. Conclusão A associação do AH com as AD-CTMs, com ou sem a membrana, não demonstrou superioridade na viabilidade celular quando comparado com SFB.

Morphometric aspects of the articular cartilage of rats treated with low-level laser therapy and exercise in a rheumatoid arthritis model

INTRODUCTION: Rheumatoid arthritis (RA) is classified as an autoimmune, chronic disease affecting diarthrodial joints and periarticular structures. OBJECTIVE: To evaluate whether low-intensity laser treatment (LLLT) and/or exercise reduce the deleterious effects of tissue in a rheumatoid arthritis model. METHODS: 128 rats were divided into two inflammatory periods: acute (7 days) and chronic (28 days) and subdivided into control, injury and treatment. The protocol with Freund's Complete Adjuvant was used in two inoculations, one intradermal and one intraarticular in the tibiofemoral joint, the control animals received saline solution. For treatment, LLLT 660 nm, 5 J/cm² was used in the sensitized joint and climbing exercise in stairways with an overload of 100 grams. After the experimental period, the animals were euthanized and the joints were prepared for morphometric analysis of the total thickness, superficial, deep, and cellular density of the articular cartilage. Generalized Linear Models with Sidak post-test were chosen. RESULTS: The control group was found to be different from the lesion group with greater joint cartilage thickness, andthe animals treated with exercise alone increased the joint cartilage compared to thecontrol group. CONCLUSION: The animals treated with laser association and exercise showed improvement in the morphometric aspects of the articular cartilage.

Experimental study on the regulation of subchondral bone plate osteoprotegerin/receptor activator of nuclear factor kappa-B ligand system by berberine to retard the development of osteoarthritis in rabbits / 中国骨伤

OBJECTIVE@#To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA).@*METHODS@#Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation.@*RESULTS@#The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01).@*CONCLUSION@#Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.

Experimental study of the response of articular cartilage surface roughness to load / 生物医学工程学杂志

Cartilage surface fibrosis is an early sign of osteoarthritis and cartilage surface damage is closely related to load. The purpose of this study was to study the relationship between cartilage surface roughness and load. By applying impact, compression and fatigue loads on fresh porcine articular cartilage, the rough value of cartilage surface was measured at an interval of 10 min each time and the change rule of roughness before and after loading was obtained. It was found that the load increased the roughness of cartilage surface and the increased value was related to the load size. The time of roughness returning to the initial condition was related to the load type and the load size. The impact load had the greatest influence on the roughness of cartilage surface, followed by the severe fatigue load, compression load and mild fatigue load. This article provides reference data for revealing the pathogenesis of early osteoarthritis and preventing and treating articular cartilage diseases.

Repair impact of vibration exercise with different frequencies on articular cartilage of rats with early knee osteoarthritis and its JNK/NF-κB, SOX9 mechanisms / 中国应用生理学杂志

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups(n=8):model control group(MC),high frequency vibration group 1 (GP1,60 Hz),high frequency vibration 2 group (GP2,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1st,4 th and 7th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2～5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher (P＜0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower(P＜0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower (P＜0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly (P＜0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower (P＜0.05 or P＜0.01). But the expressions of Sox9 mRNA and protein were significantly higher (P＜ 0.05 or P＜0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.

Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1 / 国际口腔科学杂志·英文版

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice / 国际口腔科学杂志·英文版

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Effect of Buyi Pishen acupuncture on inflammatory factor and cartilage matrix in adjuvant arthritis rats / 中国针灸

OBJECTIVE@#To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA).@*METHODS@#A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1β, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method.@*RESULTS@#Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group.@*CONCLUSION@#Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.

Progress on knee cartilage repair by knee joint distraction / 中国骨伤

Knee joint distraction is a new technology for the treatment of knee osteoarthritis in recent years. It could reduce knee pain and improve knee function, which is inseparable from the role of cartilage repair. The mechanism and influencing factors of knee joint distraction in repairing cartilage are the focus of current research. In this paper, the author reviewed literature and found that knee joint distraction could reduce knee joint load and provide a appropriate mechanical environment for cartilage repair, and it is resulting hydrostatic pressure fluctuation in the knee joint not only helps cartilage to absorb nutrients, but also promotes cartilage formation genes and inhibits cartilage matrix degrading enzyme gene expression. In addition, knee joint distraction creates conditions for synovial mesenchymal stem cells to be collected to cartilage injury, and improves ability of synovial mesenchymal stem cells to proliferate and differentiate into a chondrogenic lineage. Knee joint distraction could reduce inflammatory reaction and cartilage injury of knee joint by reducing content of inflammatory factors and inhibiting expression of inflammatory genes. At present, it is known that the factors affect repair of cartilage by knee joint distraction include, increasing weight-bearing activity and height and time of distraction is helpful for cartilage repair, male patients and patients with higher severity of knee osteoarthritis have better cartilage repair effect after knee joint distraction.The better efficacy of cartilage repair on the first year after knee joint distraction predicts a higher long-term survival rate of knee joint distraction with knee preservation. However, the research on the above hot spots is only at the initial stage and further exploration is still needed, in order to better guide clinical application of knee joint distraction.

Study on transport of small molecule rhodamine B within different layers of cartilage / 生物医学工程学杂志

The small molecule nutrients and cell growth factors required for the normal metabolism of chondrocyte mainly transport into the cartilage through free diffusion. However, the specific mass transfer law in the cartilage remains to be studied. In this study, using small molecule rhodamine B as tracer, the mass transfer models of cartilage were built under different pathways including surface pathway, lateral pathway and composite pathway. Sections of cartilage at different mass transfer times were observed by using laser confocal microscopy and the transport law of small molecules within different layers of cartilage was studied. The results showed that rhodamine B diffused into the whole cartilage layer through surface pathway within 2 h. The fluorescence intensity in the whole cartilage layer increased with the increase of mass transfer time. Compared to mass transfer of 2 h, the mean fluorescence intensity in the superficial, middle, and deep layers of cartilage increased by 1.83, 1.95, and 3.64 times, respectively, after 24 h of mass transfer. Under lateral path condition, rhodamine B was transported along the cartilage width, and the molecular transport distance increased with increasing mass transfer time. It is noted that rhodamine B could be transported to 2 mm away from cartilage side after 24 h of mass transfer. The effect of mass transfer under the composite path was better than those under the surface path and the lateral path, and especially the mass transfer in the deep layer of cartilage was improved. This study may provide a reference for the treatment and repair of cartilage injury.

Assessing the racial differences in Q angle measurements in relevance to articular cartilage of the femoral condyle: a retrospective ultrasound study / Evaluación de las diferencias raciales en las mediciones del ángulo Q en relación con el cartílago articular del cóndilo femoral: un estudio ecográfico retrospectivo

SUMMARY: The Q-angle is defined as the acute angle formed by the vectors for combined pull of the quadriceps femoris muscle and the patellar tendon. This study aimed to investigate the variations in Q angle with respect to race. Moreover, this study performed ultrasound to evaluate of the thickness of articular cartilage covering the medial and lateral femoral condyle in volunteers with an increased Q angle. The study included 487 Jordanian and 402 Malaysians with age range 18-23 years. Moreover, the study included 30 participants aged between 18 and 22 years, with a total of 15 volunteers with Q >14° and 15 patients with Q ≤14°. Both Q angle and condylar distance were measured by well-trained medical practitioners according to a well-established protocol. The thickness of articular cartilage covering the medial and lateral femoral condyle of the femoral bone was measured using ultrasound. Regardless of race, Q angle was greater in females. Furthermore, Q angle was significantly greater in Arab volunteers compared to Malay volunteers. Q angle significantly increase with increasing condylar distance in both races. Finally, the statistical analysis showed a significantly reduced thickness of articular cartilage on both medial and lateral femoral condyle (P = 0.05) in the Q >14° group. Multiple factors including race and condylar distance and even the articular cartilage of femoral condyle should be considered during the examination and management of knee fractures and condylar diseases.

RESUMEN: El ángulo Q se define como el ángulo agudo formado por los vectores de tracción combinada del músculo cuádriceps femoral y el tendón patelar. Este estudio tuvo como objetivo investigar las variaciones en el ángulo Q con respecto a la raza. Además, se realizó una ecografía para evaluar el grosor del cartílago articular que cubre los cóndilos femorales medial y lateral en voluntarios con un ángulo Q aumentado. El estudio incluyó a 487 jordanos y 402 malayos con un rango de edad de 18 a 23 años. Además, el estudio incluyó a 30 participantes con edades comprendidas entre 18 y 22 años, 15 voluntarios con Q> 14 ° y 15 pacientes con Q ≤ 14 °. Tanto el ángulo Q como la distancia condilar fueron medidos por médicos bien entrenados de acuerdo con un protocolo establecido. El grosor del cartílago articular que cubre los cóndilos femorales medial y lateral del fémur se midió mediante ecografía. Independientemente del grupo racial, el ángulo Q fue mayor en las mujeres. Además, el ángulo Q fue significativamente mayor en los voluntarios árabes en comparación con los voluntarios malayos. El ángulo Q se aumenta significativamente al incrementarse la distancia condilar en ambas grupos raciales. Finalmente, el análisis estadístico mostró una reducción significativa del grosor del cartílago articular en los cóndilos femorales medial y lateral (P = 0,05) en el grupo Q> 14. Durante la exploración y el tratamiento de las fracturas de rodilla y de las enfermedades condilares, se deben considerar múltiples factores, incluida la raza y la distancia condilar e incluso el cartílago articular del cóndilo femoral.

Ankle Osteoarthritis / Osteoartrite do tornozelo

Abstract Osteoarthritis (OA) is characterized by a chronic, progressive and irreversible degradation of the joint surface associated with joint inflammation. The main etiology of ankle OA is post-traumatic and its prevalence is higher among young and obese people. Despite advances in the treatment of fractures around the ankle, the overall risk of developing posttraumatic ankle OA after 20 years is almost 40%, especially in Weber type B and C bimalleolar fractures and in fractures involving the posterior tibial border. In talus fractures, this prevalence approaches 100%, depending on the severity of the lesion and the time of follow-up. In this context, the current understanding of the molecular signaling pathways involved in senescence and chondrocyte apoptosis is fundamental. The treatment of ankle OA is staged and guided by the classification systems and local and patient conditions. The main problems are the limited ability to regenerate articular cartilage, low blood supply, and a shortage of progenitor stem cells. The present update summarizes recent scientific evidence of post-traumatic ankle OA with a major focus on changes of the synovia, cartilage and synovial fluid; as well as the epidemiology, pathophysiology, clinical implications, treatment options and potential targets for therapeutic agents.

Resumo A osteoartrite (OA) é caracterizada por uma degradação crônica, progressiva e irreversível da superfície articular, associada a inflamação articular. A principal etiologia da OA do tornozelo é pós-traumática e sua prevalência é maior entre os jovens e obesos. Apesar dos avanços no tratamento das fraturas ao redor do tornozelo, o risco geral de desenvolver OA pós-traumática do tornozelo após 20 anos do trauma é de quase 40%; especialmente nas fraturas bimaleolares de Weber tipo B e C e fraturas envolvendo a borda tibial posterior. Nas fraturas do tálus, essa prevalência se aproxima de 100%, dependendo da gravidade da lesão e do tempo de seguimento. Nesse cenário, é fundamental a compreensão atual das vias de sinalização moleculares envolvidas na senescência e apoptose dos condrócitos. O tratamento da OA do tornozelo é estagiado e guiado pelos sistemas de classificação, condições locais e do paciente. Os principais problemas são a limitada capacidade de regeneração da cartilagem articular, o baixo suprimento de sangue e a escassez de células-tronco progenitoras. A presente atualização resume evidências científicas básicas recentes da OA póstraumática do tornozelo, com foco principal nas alterações metabólicas da sinóvia, da cartilagem e do líquido sinovial. Epidemiologia, fisiopatologia, implicações clínicas, e opções de tratamento são também discutidas.

Larger Chondral Lesions Treated with Collagen Membrane - Matrix-Induced Autologous Chondrogenesis - Show Larger Increase in Clinical Scores / Lesões condrais maiores tratadas com uso de membrana de colágeno - condrogênese autóloga induzida por matriz - apresentam maior aumento nos escores clínicos

Abstract Objective To evaluate clinically and radiologically the results of the treatment of chondral lesions using collagen membrane - autologous matrix-induced chondrogenesis (AMIC). Methods This is a series of observational cases, in which 15 patients undergoing AMIC were analyzed. The clinical evaluation was made by comparing the Lysholm and International Knee Document Commitee (IKDC) scores in the pre- and postoperative period of 12 months, and radiological evaluation using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score in the same postoperative period. Results The mean age of the patients was 39.2 years old, and the mean size of the chondral lesions was 1.55cm2. There was a significant improvement in clinical scores, with a mean increase of 24.6 points on Lysholm and of 24.3 on IKDC after 12 months. In the radiological evaluation, MOCART had a mean of 65 points. It was observed that the larger the size of the lesion, the greater the improvement in scores. Conclusion Evaluating subjective clinical scores, the treatment of chondral lesions with the collagen membrane showed good results, as well as the evaluation of MOCART, with greater benefit in larger lesions.

Resumo Objetivo Avaliar clínica e radiologicamente os resultados do tratamento das lesões condrais com a membrana de colágeno - condrogênese autóloga induzida por matriz. Métodos Trata-se de uma série de casos observacional, na qual foram analisados 15 pacientes submetidos a condrogênese autóloga induzida por matriz. A avaliação clínica foi feita comparando os escores de Lysholm e International Knee Document Commitee (IKDC, na sigla em inglês) no pré- e pós-operatório de 12 meses, e avaliação radiológica através do escore de Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART, na sigla em inglês) no mesmo período de pós-operatório. Resultados A média de idade dos pacientes foi 39,2 anos, e a média do tamanho das lesões condrais foi de 1,55cm2. Houve uma melhora significativa nos escores clínicos, com média de aumento de 24,6 pontos no Lysholm e de 24,3 no IKDC, após 12 meses. Na avaliação radiológica, o MOCART teve média de 65 pontos. Observou-se que quanto maior o tamanho da lesão, maior foi a melhora nos escores. Conclusão Avaliando escores clínicos subjetivos, o tratamento das lesões condrais com a membrana de colágeno mostrou bons resultados, assim como a avaliação de MOCART, com maior benefício em lesões maiores.