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2.
Biomed Res Int ; 2022: 4117520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509713

RESUMO

Osteoarthritis (OA) is one of the age-related diseases and is highly present on the knees. Obesity and mechanical injuries as a risk factor of OA are attributed to cartilage disintegration, joint loading, and inflammation. This study is aimed at investigating the effects of seahorse protein hydrolysate (SH) on posttraumatic osteoarthritis in an obesity rat. The OA model was developed by anterior cruciate ligament transection with medial meniscectomy in a high-fat diet- (HFD-) induced obesity rat model. The male Sprague-Dawley rats were fed a HFD for 6 weeks before OA surgery. The OA rats were treated with oral gavage by 4, 8, or 20 mg/kg of body weight of SH for 6 weeks of treatment. The expressions of plasma proinflammatory factors, C-telopeptide of type II collagen, and matrix metalloproteinase- (MMP-) 3 and MMP-13 were reduced by SH treatment. Plasma superoxide dismutase and glutathione peroxidase activities were enhanced by SH. SH also relieved the pain of the knee joint and swelling as well as decreased proteoglycan loss in the knee articular cartilage caused by osteoarthritis. Based on these results, SH suppressed proinflammatory factors and attenuated cartilage degradation and pain in the OA model. Therefore, seahorse protein hydrolysate might be a potential opportunity for improving the development of osteoarthritis.


Assuntos
Cartilagem Articular , Osteoartrite , Smegmamorpha , Animais , Cartilagem Articular/metabolismo , Modelos Animais de Doenças , Masculino , Obesidade/complicações , Obesidade/metabolismo , Osteoartrite/metabolismo , Dor/metabolismo , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Sprague-Dawley
3.
Nat Commun ; 13(1): 2447, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508470

RESUMO

Damaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) "difficult-to-treat". Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.


Assuntos
Cartilagem Articular , MicroRNAs , Osteoartrite , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/metabolismo , Homeostase , Humanos , Metaloproteinase 13 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/metabolismo
4.
Comput Math Methods Med ; 2022: 7643487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529263

RESUMO

The objective of this study was to investigate the application effect of deep learning model combined with different magnetic resonance imaging (MRI) sequences in the evaluation of cartilage injury of knee osteoarthritis (KOA). Specifically, an image superresolution algorithm based on an improved multiscale wide residual network model was proposed and compared with the single-shot multibox detector (SSD) algorithm, superresolution convolutional neural network (SRCNN) algorithm, and enhanced deep superresolution (EDSR) algorithm. Meanwhile, 104 patients with KOA diagnosed with cartilage injury were selected as the research subjects and underwent MRI scans, and the diagnostic performance of different MRI sequences was analyzed using arthroscopic results as the gold standard. It was found that the image reconstructed by the model in this study was clear enough, with minimum noise and artifacts, and the overall quality was better than that processed by other algorithms. Arthroscopic analysis found that grade I and grade II lesions concentrated on patella (26) and femoral trochlear (15). In addition to involving the patella and femoral trochlea, grade III and grade IV lesions gradually developed into the medial and lateral articular cartilage. The 3D-DS-WE sequence was found to be the best sequence for diagnosing KOA injury, with high diagnostic accuracy of over 95% in grade IV lesions. The consistency test showed that the 3D-DESS-WE sequence and T2∗ mapping sequence had a strong consistency with the results of arthroscopy, and the Kappa consistency test values were 0.748 and 0.682, respectively. In conclusion, MRI based on deep learning could clearly show the cartilage lesions of KOA. Of different MRI sequences, 3D-DS-WE sequence and T2∗ mapping sequence showed the best diagnosis results for different degrees of KOA injury.


Assuntos
Cartilagem Articular , Aprendizado Profundo , Traumatismos do Joelho , Osteoartrite do Joelho , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Cartilagem Articular/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia
5.
Zhongguo Gu Shang ; 35(5): 464-9, 2022 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-35535536

RESUMO

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.


Assuntos
Berberina , Conservadores da Densidade Óssea , Cartilagem Articular , Osteoartrite , Animais , Berberina/metabolismo , Berberina/farmacologia , Berberina/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Placas Ósseas , Humanos , Ligantes , Masculino , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , RNA Mensageiro/uso terapêutico , Coelhos
6.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(2): 347-352, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35523556

RESUMO

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.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Fadiga , Osteoartrite/patologia , Pressão , Suínos
7.
J Orthop Surg Res ; 17(1): 195, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365162

RESUMO

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative disease, its main characteristic involves articular cartilage destruction and inflammation response, absent of effective medical treatment. Our current research aimed to explore anti-inflammatory effect of kirenol, a diterpenoid natural product compound, in the development of OA and its potential molecular mechanism through in vitro and in vivo study. METHODS: In vitro, chondrocytes were pretreated with kirenol for 2 h before IL-1ß stimulation. Production of NO, PGE2, TNF-α, IL-6, aggrecan, collagen-II, MMP13and ADAMTS5 were evaluated by the Griess reaction and ELISAs. The mRNA (aggrecan and collagen-II) and protein expression (COX-2, iNOS, P65, IκB, PI3K, AKT) were measured by qRT-PCR and Western blot respectively. Immunofluorescence was used to assess the expression of collagen-II and P65. The in vivo effect of kirenol was evaluated in mice OA models induced by destabilization of the medial meniscus (DMM). RESULTS: We found that kirenol inhibited IL-1ß-induced expression of NO, PGE2, TNF-α, IL-6, COX-2, iNOS, ADAMTS-5. Besides, kirenol remarkably decreased IL-1ß-induced degradation of aggrecan and collagen-II. Furthermore, kirenol significantly inhibited IL-1ß-induced phosphorylation of PI3K/Akt and NF-κB signaling. In vivo, the cartilage in kirenol-treated mice exhibited less cartilage degradation and lower OARSI scores. CONCLUSIONS: Taken together, the results of this study provide potent evidence that kirenol could be utilized as a potentially therapeutic agent in prevention and treatment of OA.


Assuntos
Cartilagem Articular , Diterpenos , Osteoartrite , Animais , Células Cultivadas , Diterpenos/uso terapêutico , Camundongos , Osteoartrite/tratamento farmacológico , Fosfatidilinositol 3-Quinases
8.
Sci Rep ; 12(1): 6694, 2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461315

RESUMO

Early diagnosis of osteoarthritis (OA), before the onset of irreversible changes is crucial for understanding the disease process and identifying potential disease-modifying treatments from the earliest stage. OA is a whole joint disease and affects both cartilage and the underlying subchondral bone. However, spatial relationships between cartilage lesion severity (CLS) and microstructural changes in subchondral plate and trabecular bone remain elusive. Herein, we collected femoral heads from hip arthroplasty for primary osteoarthritis (n = 7) and femoral neck fracture (n = 6; non-OA controls) cases. Samples were regionally assessed for cartilage lesions by visual inspection using Outerbridge classification and entire femoral heads were micro-CT scanned. Scans of each femoral head were divided into 4 quadrants followed by morphometric analysis of subchondral plate and trabecular bone in each quadrant. Principal component analysis (PCA), a data reduction method, was employed to assess differences between OA and non-OA samples, and spatial relationship between CLS and subchondral bone changes. Mapping of the trabecular bone microstructure in OA patients with low CLS revealed trabecular organisation resembling non-OA patients, whereas clear differences were identifiable in subchondral plate architecture. The OA-related changes in subchondral plate architecture were summarised in the first principle component (PC1) which correlated with CLS in all quadrants, whilst by comparison such associations in trabecular bone were most prominent in the higher weight-bearing regions of the femoral head. Greater articular cartilage deterioration in OA was regionally-linked with lower BV/TV, TMD and thickness, and greater BS/BV and porosity in the subchondral plate; and with thinner, less separated trabeculae with greater TMD and BS/BV in the trabecular bone. Our findings suggest that impairment of subchondral bone microstructure in early stage of OA is more readily discernible in the cortical plate and that morphological characterisation of the femoral head bone microstructure may allow for earlier OA diagnosis and monitoring of progression.


Assuntos
Cartilagem Articular , Osteoartrite , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Fêmur/patologia , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Humanos , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Microtomografia por Raio-X/métodos
9.
J Biomed Nanotechnol ; 18(2): 504-511, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35484732

RESUMO

Objective: Since the benefits of Nano-material usage have been well documented in orthopedic surgery, this study was conducted to explore the effect of polyvinyl alcohol/nano-hydroxyapatite/polyamide 66 (PVA/n-HA/P66) on repairing of traumatic cartilage defects in rabbit knee joint. Methods: New Zealand white rabbits were used to make a rabbit knee traumatic cartilage defect animal model. All rabbits were randomly located in three groups. Group-A (PVA/n-HA+PA66 implanted in cartilage defects); Group-B (HA nanospheres implanted in cartilage defects)/Gelatin sponge composite scaffold); Group-C (only cartilage defect without implant). The repairment of articular cartilage defects and the general observation were studied by using pathological staining and gene expression of collagen using RT-PCR after 12 weeks. Results: After 12 weeks, we observed a small amount of fibrous tissue growth in group C without soft cell filling. The repaired tissue in group B was stained with immunohistochemical and toluidine blue staining for collagen and type II collagen is positive, but chondrocyte structure is more visible. The relative mRNA expression of type II collagen was higher in group B in comparison to other groups. The results of the Wakitani score were 5.50±2.59 for group A, 8.83±2.79 for group B, 11.50±1.05 for group C. Results showed no significant difference between group B and C; however, significant differences were found in the scoring results between groups A and B, and between-group A and C. Conclusion: This study showed the high effectiveness of PVA/n-HA+PA66 in the treatment of cartilage defects through increasing the expression of type II collagen.


Assuntos
Cartilagem Articular , Animais , Cartilagem Articular/patologia , Cartilagem Articular/cirurgia , Colágeno/farmacologia , Colágeno Tipo II/genética , Colágeno Tipo II/farmacologia , Modelos Teóricos , Coelhos , Regeneração
10.
Malays J Pathol ; 44(1): 1-18, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35484882

RESUMO

Wnt signalling plays an important role in bone and cartilage metabolism. Activation of Wnt signalling promotes bone formation but cartilage degradation. Sclerostin (SOST) can inhibit Wnt signalling. It is expressed by chondrocytes in the articular cartilage and osteocytes in the subchondral bone. Since osteoarthritis (OA) is a joint degenerative disease involving both bone and joint compartments, SOST may have a role in mediating the progression of this disease. This review examined the current literature on the role of SOST in the pathogenesis of OA and its usefulness as a biomarker of OA. Most studies agree that SOST is upregulated as a rescue mechanism in OA to prevent further degenerative changes of the joint. It antagonises inflammation-induced cartilage catabolism while preserving chondrocyte anabolic activities. It also prevents abnormal bone mineralisation and osteophyte formation. However, studies on the performance of SOST as a biomarker to detect and stage OA are limited. Further studies are required to determine whether SOST can be a biomarker or therapeutic target for OA.


Assuntos
Cartilagem Articular , Osteoartrite , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Condrócitos/metabolismo , Condrócitos/patologia , Humanos , Osteoartrite/metabolismo , Osteoartrite/patologia
11.
Stem Cell Res Ther ; 13(1): 168, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477424

RESUMO

BACKGROUND: Fully functional regeneration of skeletal defects by multipotent progenitor cells requires that differentiating cells gain the specific mechano-competence needed in the target tissue. Using cartilage neogenesis as an example, we asked whether proper phenotypic differentiation of mesenchymal stromal cells (MSC) into chondrocytes in vitro will install the adequate biological mechano-competence of native articular chondrocytes (AC). METHODS: The mechano-competence of human MSC- and AC-derived neocartilage was compared during differentiation for up to 35 days. The neocartilage layer was subjected to physiologic dynamic loading in a custom-designed bioreactor and assayed for mechano-sensitive gene and pathway activation, extracellular matrix (ECM) synthesis by radiolabel incorporation, nitric oxide (NO) and prostaglandin E2 (PGE2) production. Input from different pathways was tested by application of agonists or antagonists. RESULTS: MSC and AC formed neocartilage of similar proteoglycan content with a hardness close to native tissue. Mechano-stimulation on day 21 and 35 induced a similar upregulation of mechano-response genes, ERK phosphorylation, NO production and PGE2 release in both groups, indicating an overall similar transduction of external mechanical signals. However, while AC maintained or enhanced proteoglycan synthesis after loading dependent on tissue maturity, ECM synthesis was always significantly disturbed by loading in MSC-derived neocartilage. This was accompanied by significantly higher COX2 and BMP2 background expression, > 100-fold higher PGE2 production and a weaker SOX9 stimulation in response to loading in MSC-derived neocartilage. Anabolic BMP-pathway activity was not rate limiting for ECM synthesis after loading in both groups. However, NFκB activation mimicked the negative loading effects and enhanced PGE2 production while inhibition of catabolic NFκB signaling rescued the load-induced negative effects on ECM synthesis in MSC-derived neocartilage. CONCLUSIONS: MSC-derived chondrocytes showed a higher vulnerability to be disturbed by loading despite proper differentiation and did not acquire an AC-like mechano-competence to cope with the mechanical stress of a physiologic loading protocol. Managing catabolic NFκB influences was one important adaptation to install a mechano-resistance closer to AC-derived neocartilage. This new knowledge asks for a more functional adaptation of MSC chondrogenesis, novel pharmacologic co-treatment strategies for MSC-based clinical cartilage repair strategies and may aid a more rational design of physical rehabilitation therapy after AC- versus MSC-based surgical cartilage intervention.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Prostaglandinas E/metabolismo , Proteoglicanas/metabolismo
12.
Sci Rep ; 12(1): 6844, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477722

RESUMO

Knowledge of the anatomy of the anterior cruciate ligament (ACL) is important to understand the function and pathology of the knee joint. However, on the tibial side of ACL, its structural relationships with the articular cartilage and lateral meniscus remain unclear. Furthermore, conventional research methods are limited to analyzing the bone attachments. We provide a comprehensive, three-dimensional anatomical description of the tibial side of the ACL that questions the principle that "a ligament is necessarily a structure connecting a bone to another bone." In our study, 11 knees from 6 cadavers were used for macroscopic anatomical examinations, serial-section histological analyses, and three-dimensional reconstructions. The attachments of the tibial side of ACL consisted of attachments to the bone (102.6 ± 27.5 mm2), articular cartilage (40.9 ± 13.6 mm2), and lateral meniscus (6.5 ± 4.6 mm2), suggesting that the ACL has close structural relationships with the articular cartilage and lateral meniscus. Our study demonstrates that the tibial side of the ACL is not attached to the bone surface only and provides new perspectives on ligamentous attachments. Considering its attachment to the articular cartilage would enable more accurate functional evaluations of the mechanical tensioning of the ACL.


Assuntos
Ligamento Cruzado Anterior , Cartilagem Articular , Ligamento Cruzado Anterior/patologia , Articulação do Joelho/anatomia & histologia , Meniscos Tibiais/anatomia & histologia , Tíbia/patologia
13.
Vet J ; 282: 105825, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35381440

RESUMO

Osteochondrosis is commonly encountered in young horses, with welfare, performance, and economic effects. Consequently, pre-purchase radiographic screening for osteochondrosis is routinely performed. Ultrasonographic examination of articular cartilage and osteochondrosis lesions are described in the literature with many case series or single case reports published. This systematic review was undertaken to examine the evidence for using ultrasonography in comparison to traditional radiography, arthroscopy or necropsy findings in the detection of osteochondrosis. The systematic review identified a paucity of studies in which there was marked variation in the populations, sample size, methods and results reported. Currently, there is no strong evidence confirming the diagnostic accuracy and validity of ultrasonography in the detection of osteochondral lesions in the relevant joints in horses.


Assuntos
Cartilagem Articular , Doenças dos Cavalos , Osteocondrose , Animais , Cartilagem Articular/patologia , Doenças dos Cavalos/diagnóstico , Cavalos , Osteocondrose/diagnóstico por imagem , Osteocondrose/patologia , Osteocondrose/veterinária , Radiografia , Ultrassonografia/veterinária
14.
Orthop Surg ; 14(5): 946-954, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35441488

RESUMO

OBJECTIVE: To observe expression of CD38, a key modulator of nicotinamide dinucleotide (NAD+) metabolism in mice with knee osteoarthritis, and protective effect of CD38 inhibition during the osteoarthritis (OA) development. METHOD: The destabilization of the medial meniscus (DMM) model was performed in mice to mimic the process of OA. Immunofluorescence of CD38 was performed to evaluate its response during the OA process. Limb bud-derived mesenchymal cells were isolated for micromass culture. 100 nM or 1 µM CD38 inhibitor (78c) treatment for 14 days and CD38 sgRNA infection were then used to explore the effects of chondrogenic differentiation via Alcian blue staining. The expressions of chondrogenic markers were detected using RT-PCR and Western blot. To explore the protective effect of CD38 inhibitor on cartilage degradation during OA in vivo, a CD38 inhibitor was injected into the knee joint after DMM operations. Micro-CT analysis and Safranin O-fast green staining were used to evaluate subchondral bone micro-architecture changes and cartilage degeneration. RESULTS: Compared to the control group, the CD38 expression in superficial cartilage was obviously increased in DMM group (P < 0.05). During the normal chondrogenic differentiation, the extracellular matrix formed and expression of Sox9, Col2, aggrecan increased apparently while CD38 expression decreased, which could be reversed with ablation of CD38 in limb bud-derived mesenchymal cells. Consistent with findings in vitro, CD38 blockage via CD38 inhibitor injection protected against osteosclerosis in medial subchondral bone and cartilage degeneration in DMM-induced experimental mice. Compared to the Sham group, DMM mice showed significantly increased values of BV and BV/TV in subchondral bone (P < 0.05) and Mankin score, which could be rescued by 78c treatment (P < 0.05). Also the CD38 inhibitor contributed to homeostasis of anabolism and catabolism by upregulating Sox9, Col2, aggrecan and downregulating Runx2, Col10 and Mmp13. CONCLUSION: This study primarily implicates CD38 as an important regulator of chondrogenic differentiation. Inhibition of CD38 demonstrated protection against cartilage degeneration, which suggests that CD38 could be a potential therapeutic target for OA.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Agrecanas , Animais , Condrócitos , Modelos Animais de Doenças , Homeostase , Humanos , Meniscos Tibiais/cirurgia , Camundongos , Osteoartrite do Joelho/metabolismo
15.
Am J Sports Med ; 50(4): 951-961, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35373606

RESUMO

BACKGROUND: Patients undergoing anterior cruciate ligament reconstruction (ACLR) are at an increased risk for posttraumatic osteoarthritis (PTOA). While we have previously shown that meniscal treatment with ACLR predicts more radiographic PTOA at 2 to 3 years postoperatively, there are a limited number of similar studies that have assessed cartilage directly with magnetic resonance imaging (MRI). HYPOTHESIS: Meniscal repair or partial meniscectomy at the time of ACLR independently predicts more articular cartilage damage on 2- to 3-year postoperative MRI compared with a healthy meniscus or a stable untreated tear. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A consecutive series of patients undergoing ACLR from 1 site within the prospective, nested Multicenter Orthopaedic Outcomes Network (MOON) cohort underwent bilateral knee MRI at 2 to 3 years postoperatively. Patients were aged <36 years without previous knee injuries, were injured while playing sports, and had no history of concomitant ligament surgery or contralateral knee surgery. MRI scans were graded by a board-certified musculoskeletal radiologist using the modified MRI Osteoarthritis Knee Score (MOAKS). A proportional odds logistic regression model was built to predict a MOAKS-based cartilage damage score (CDS) relative to the contralateral control knee for each compartment as well as for the whole knee, pooled by meniscal treatment, while controlling for sex, age, body mass index, baseline Marx activity score, and baseline operative cartilage grade. For analysis, meniscal injuries surgically treated with partial meniscectomy or meniscal repair were grouped together. RESULTS: The cohort included 60 patients (32 female; median age, 18.7 years). Concomitant meniscal treatment at the time of index ACLR was performed in 17 medial menisci (13 meniscal repair and 4 partial meniscectomy) and 27 lateral menisci (3 meniscal repair and 24 partial meniscectomy). Articular cartilage damage was worse in the ipsilateral reconstructed knee (P < .001). A meniscal injury requiring surgical treatment with ACLR predicted a worse CDS for medial meniscal treatment (medial compartment CDS: P = .005; whole joint CDS: P < .001) and lateral meniscal treatment (lateral compartment CDS: P = .038; whole joint CDS: P = .863). Other predictors of a worse relative CDS included age for the medial compartment (P < .001), surgically observed articular cartilage damage for the patellofemoral compartment (P = .048), and body mass index (P = .007) and age (P = .020) for the whole joint. CONCLUSION: A meniscal injury requiring surgical treatment with partial meniscectomy or meniscal repair at the time of ACLR predicted worse articular cartilage damage on MRI at 2 to 3 years after surgery. Further research is required to differentiate between the effects of partial meniscectomy and meniscal repair.


Assuntos
Lesões do Ligamento Cruzado Anterior , Cartilagem Articular , Menisco , Ortopedia , Adolescente , Adulto , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Cartilagem Articular/cirurgia , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Menisco/diagnóstico por imagem , Menisco/cirurgia , Estudos Prospectivos
16.
Chem Biol Interact ; 360: 109921, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35385713

RESUMO

ITCH is an E3 ubiquitin ligase associated with some inflammatory diseases, but its role in osteoarthritis (OA) remains to be explored. Here, we investigated the effects of ITCH in OA-induced chondrocyte damage and its potential mechanisms. Here, we found that ITCH was downregulated, while JAG1 was upregulated in OA tissues compared to normal cartilaginous tissues. And primary human chondrocytes were induced by LPS to simulate OA condition. Overexpressing ITCH or silencing JAG1 promoted proliferation, and restrained apoptosis, inflammation and extracellular matrix (ECM) degradation in LPS-stimulated chondrocytes. Mechanistically, ITCH bound to JAG1 protein through the WW-PPXY motif and degraded it via K48 ubiquitination. JAG1 overexpression reversed the protective effect of ITCH on LPS-induced chondrocyte damage. ITCH prevented LPS-caused Notch1 signaling activation by suppressing JAG1. Furthermore, GSI (a Notch specific inhibitor) abrogated the effects of ITCH knockdown on chondrocyte injury. Additionally, a mouse OA model was established by destabilization of the medial meniscus operation, and H&E and Safranin O-fast green staining was used to evaluate articular cartilage damage. And ITCH overexpression alleviated OA-induced articular cartilage damage in vivo. In conclusion, ITCH mitigated LPS-induced chondrocyte injury and OA-induced articular cartilage damage through attenuating Notch1 pathway activation by degrading JAG1 via ubiquitination, which provides a novel strategy for the treatment of OA.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Apoptose , Cartilagem Articular/metabolismo , Condrócitos , Lipopolissacarídeos/farmacologia , Camundongos , Osteoartrite/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
17.
Am J Phys Med Rehabil ; 101(5): 433-438, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35444153

RESUMO

OBJECTIVE: We aimed to elucidate the association of lower limb muscle strength with the volume loss of cartilages/menisci for patients with mild and moderate knee osteoarthritis. DESIGN: One hundred seventy individuals with mild and moderate knee osteoarthritis were included from the Osteoarthritis Initiative database. Five muscle strength variables were measured from isometric strength test. The measurement of volume on medial and lateral menisci and seven subregional cartilages from knee magnetic resonance scans were used for assessing 2-yr osteoarthritis progression. RESULTS: Along with the decreased lower limb muscle strength, the volume of patellar cartilage, medial meniscus, and lateral meniscus decreased more than cartilage on tibia and weight-bearing femoral condyle. However, the cartilage volume on the entire medial and lateral femoral condyle increased significantly. The maximum quadricep strength was the most sensitive muscle strength variable, and we found that it was more positively correlated with lateral meniscus volume than with other subregions at baseline and 24-mo follow-up. CONCLUSIONS: This study shows the relationship between lower limb muscle strength and volumes of cartilage and meniscus for patients with mild and moderate knee osteoarthritis. In addition, our study indicates a biomechanical mechanism of quadricep strength and meniscus-related knee dynamic stability in progression of mild-to-moderate knee osteoarthritis.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Humanos , Articulação do Joelho , Extremidade Inferior , Imageamento por Ressonância Magnética , Meniscos Tibiais , Força Muscular , Osteoartrite do Joelho/diagnóstico por imagem
18.
Sci Rep ; 12(1): 6434, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440750

RESUMO

The effect of physical activity on serum cartilage biomarkers is largely unknown. The purpose of the study was to systematically analyze the acute effect of two frequently used exercise interventions (running and jumping) on the correlation of seven serum biomarkers that reflect cartilage extracellular matrix metabolism. Fifteen healthy male volunteers (26 ± 4 years, 181 ± 4 cm, 77 ± 6 kg) participated in the repeated measurement study. In session 1, the participants accomplished 15 × 15 series of reactive jumps within 30 min. In session 2, they ran on a treadmill (2.2 m/s) for 30 min. Before and after both exercise protocols, four blood samples were drawn separated by 30 min intervals. Serum concentrations of seven biomarkers were determined: COMP, MMP-3, MMP-9, YKL-40, resistin, Coll2-1 and Coll2-1 NO2. All biomarkers demonstrated an acute response to mechanical loading. Both the COMP and MMP-3 responses were significantly (p = 0.040 and p = 0.007) different between running and jumping (COMP: jumping + 31%, running + 37%; MMP-3: jumping + 14%, running + 78%). Resistin increased only significantly (p < 0.001) after running, and Coll2-1 NO2 increased significantly (p = 0.001) only after jumping. Significant correlations between the biomarkers were detected. The relationships between individual serum biomarker concentrations may reflect the complex interactions between degrading enzymes and their substrates in ECM homeostasis.


Assuntos
Cartilagem Articular , Corrida , Biomarcadores , Cartilagem , Proteína de Matriz Oligomérica de Cartilagem , Humanos , Masculino , Metaloproteinase 3 da Matriz , Dióxido de Nitrogênio , Resistina , Corrida/fisiologia
19.
Phytomedicine ; 100: 154071, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35378415

RESUMO

BACKGROUND: Osteoarthritis (OA) is a difficult disease but the clinic lacks effective therapy. As a classic formula of traditional Chinese medicine (TCM), Fuzi decoction (FZD) has been clinically applied for treating OA-related syndromes, but its anti-OA efficacy and mechanism remain unclear. PURPOSE: To experimentally and clinically determine the anti-OA efficacy of FZD and clarify the underlying mechanism. METHODS: UPLC/MS/MS was applied to identify the main components of FZD. A monoiodoacetate (MIA)-induced OA rat model was employed to evaluate the in vivo efficacy of FZD against OA, by using pain behavior assessment, histopathological observation, and immunohistochemical analysis. Primary rat chondrocytes were isolated to determine the in vitro effects of FZD by using cell viability assay, wound healing assay, and real-time PCR (qPCR) analysis on anabolic/catabolic mRNA expressions. RNA sequencing (RNA-seq) and network pharmacology analysis were conducted and the overlapping data were used to predict the mechanism of FZD, followed by verification with qPCR and Western blot assays. Finally, a retrospective analysis was performed to confirm FZD's efficacy and safety in OA patients. RESULTS: The UPLC/MS/MS result showed that FZD contained atractylenolide I, benzoylhypaconitine, benzoylmesaconitine, benzoylaconitine, hypaconitine, mesaconitine, aconitine, lobetyolin, paeoniflorin, and pachymic acid. The in vivo data showed that FZD restored the cartilage degeneration in MIA-induced OA rats by ameliorating pain behavior parameters, recovering histopathological alterations, benefitting cartilage anabolism (up-regulating Col2 expression), and suppressing catabolism (down-regulating MMP13 and Col10 expressions). The in vitro data showed that FZD increased cell viability and wound healing capacity of chondrocytes, and restored the altered expressions of anabolic and catabolic genes of chondrocytes. The overlapping results of RNA-seq and network pharmacology analysis suggested that PI3K/Akt signaling mediated the anti-OA mechanism of FZD, which was verified by qPCR and Western blot experiments. Clinically, the anti-OA efficacy and safety of FZD were confirmed by the retrospective analysis on OA patients. CONCLUSION: The scientific innovation of this study was the determination of anti-OA efficacy of FZD by experimental and clinical evidence and the discovery of its mechanism by integrated RNA-seq, network pharmacology, and molecular experiments, which suggests FZD as a promising TCM agency for OA treatment.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Cartilagem , Diterpenos , Medicamentos de Ervas Chinesas , Humanos , Osteoartrite/patologia , Dor/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Estudos Retrospectivos , Transdução de Sinais , Espectrometria de Massas em Tandem
20.
J Colloid Interface Sci ; 619: 207-218, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35397456

RESUMO

Due to its high molecular weight and viscosity, hyaluronic acid (HA) is widely used for viscosupplementation to provide joint pain relief in osteoarthritis. However, this benefit is temporary due to poor adhesion of HA on articular surfaces. In this study, we therefore conjugated HA with dopamine to form HADN, which made the HA adhesive while retaining its viscosity enhancement capacity. We hypothesized that HADN could enhance cartilage lubrication through adsorption onto the exposed collagen type II network and repair the lamina splendens. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine. Analysis of Magnetic Resonance (NMR) and Ultraviolet spectrophotometry (Uv-vis) showed that HADN was successfully synthesized. Adsorption of HADN on collagen was demonstrated using Quartz crystal microbalance with dissipation (QCM-D). Ex vivo tribological tests including measurement of coefficient of friction (COF), dynamic creep, in stance (40 N) and swing (4 N) phases of gait cycle indicated adequate protection of cartilage by HADN with higher lubrication compared to HA alone. HADN solution at the cartilage-glass sliding interface not only retains the same viscosity as HA and provides fluid film lubrication, but also ensures better boundary lubrication through adsorption. To confirm the cartilage surface protection of HADN, we visualized cartilage wear using optical coherence tomography (OCT) and atomic force microscopy (AFM).


Assuntos
Cartilagem Articular , Cartilagem Articular/química , Dopamina/análise , Fricção , Ácido Hialurônico/química , Injeções Intra-Articulares , Lubrificação , Líquido Sinovial/química
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