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Objective: To investigate the expressions of cartilage degenerative related genes in meniscus, and to evaluate the potential effect of meniscal damage on cartilage degeneration, and to analyze the relationship between microRNAs (miRNAs) expression and cartilage degeneration., Methods: Meniscal tissue was collected from 5 patients undergoing partial meniscectomy between September 2012 and October 2013 (experimental group), and normally meniscal tissue without tearing from amputees was used as controls (control group). Pathological changes of menisci were observed; and real-time fluorescent quatitative PCR was performed to examine the relative expression levels of cartilage degenerative related genes and miRNAs: Aggrecan (ACAN), type X collagen (COL10A1), matrix metalloproteinases 13 (MMP-13), CCAAT enhancer binding protein β (CEBP-β), a disintegrin and metalloproteinase with thrombospondinmotif 5 (ADAMTS-5), miR-193b, miR-92a, and miR-455-3p in meniscus., Results: There were varying degrees of degenerative pathological changes in torn meniscus of experimental group. Compared with normal meniscus of control group, the expression of ACAN was decreased, while the expressions of COL10A1, CEBP-β, ADAMTS-5, and MMP-13 were increased in torn meniscus of experimental group; and significant difference was found (P < 0.05) except ACAN and MMP-13 (P > 0.05). The expressions of miR-92a, miR-455-3p, and miR-193b in torn meniscus of experimental group were significantly higher than those in normal meniscus of control group (P < 0.05)., Conclusion: Meniscal tissue has the intrinsic tendency of degeration after meniscus tear. The torn meniscus has greater stimulative impact on cartilage degeneration than normally morphological meniscus without tearing. The cartilage degenerative related miRNAs, including miR-193b, miR-92a, and miR-455-3p may contribute to the up-regulation of osteoarthritis.

Objectives: Osteoarthritis (OA) is a degenerative disease causing the progressive destruction of articular cartilage; however, the aetiology has not yet been elucidated. Circular RNAs (circRNAs) are reportedly involved in cartilage degeneration and OA development. In the present study, we identified that circNFIX regulates chondrogenesis and cartilage homeostasis. Materials and Methods: Microarray analysis was performed to explore circRNA expression during the chondrogenic differentiation of human adipose‐drived stem cells (hADSCs). CircNFIX expression was determined using quantitative reverse transcription‐polymerase chain reaction and in situ hybridization. Gain‐ and loss‐of‐function assays were performed to validate the role of circNFIX in cartilage homeostasis. RNA pull‐down, Argonaute2‐RNA immunoprecipitation and luciferase reporter assays were performed to evaluate the interactions among circNFIX, miR758‐3p and KDM6A. Results: CircNFIX expression was upregulated in the early and middle stages, whereas downregulated in the late stage of hADSC chondrogenesis. CircNFIX inhibition attenuated hADSC chondrogenesis. CircNFIX was remarkably downregulated in OA samples, circNFIX overexpression protected against chondrocyte degradation and alleviated OA progression in the destabilization of the medial meniscus OA model. Mechanistically, circNFIX acted as a sponge of miR758‐3p and played a role in the chondrogenesis and chondrocyte degeneration by targeting the miR‐758‐3p/KDM6A axis. Conclusions: Our results revealed a key role of circNFIX in chondrogenesis and cartilage homeostasis, which may provide a potential therapeutic strategy for OA treatment. [ABSTRACT FROM AUTHOR]

Objectives: Aberrations in exosomal circular RNA (circRNA) expression have been identified in various human diseases. In this study, we investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA). This study aimed to elucidate the specific MSC-derived exosomal circRNAs responsible for MSC-mediated chondrogenic differentiation using human bone marrow-derived MSCs (hMSCs) and a destabilization of the medial meniscus (DMM) mouse model of OA. Methods: Exosomal circRNA deep sequencing was performed to evaluate the expression of circRNAs in human bone marrow-derived MSCs (hMSCs) induced to undergo chondrogenesis from day 0 to day 21. The regulatory and functional roles of exosomal circRNA_0001236 were examined on day 21 after inducing chondrogenesis in hMSCs and were validated in vitro and in vivo. The downstream target of circRNA_0001236 was also explored in vitro and in vivo using bioinformatics analyses. A luciferase reporter assay was used to evaluate the interaction between circRNA_0001236 and miR-3677-3p as well as the target gene sex-determining region Y-box 9 (Sox9). The function and mechanism of exosomal circRNA_0001236 in OA were explored in the DMM mouse model. Results: Upregulation of exosomal circRNA_0001236 enhanced the expression of Col2a1 and Sox9 but inhibited that of MMP13 in hMSCs induced to undergo chondrogenesis. Moreover, circRNA_0001236 acted as an miR-3677-3p sponge and functioned in human chondrocytes via targeting miR-3677-3p and Sox9. Intra-articular injection of exosomal circRNA_0001236 attenuated OA in the DMM mouse model. Conclusions: Our results reveal an important role for a novel exosomal circRNA_0001236 in chondrogenic differentiation. Overexpression of exosomal circRNA_0001236 promoted cartilage-specific gene and protein expression through the miR-3677-3p/Sox9 axis. Thus, circRNA_0001236-overexpressing exosomes may alleviate cartilage degradation, suppressing OA progression and enhancing cartilage repair. Our findings provide a potentially effective therapeutic strategy for treating OA. [ABSTRACT FROM AUTHOR]

• Osteoarthritis (OA) is the most common form of age-related arthritis and is characterized by low-grade inflammation and metabolic dysfunction. • Aberrant chondrocyte metabolism is a response to changes in the inflammatory microenvironment and may play a key role in cartilage degeneration and OA progression. • Under conditions of environmental stress, chondrocytes shift from oxidative phosphorylation to glycolysis, a process regulated by the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways. • Metabolic changes in chondrocytes and other cells in the synovial joint could be a target for future therapeutic interventions. • Future research should place greater emphasis on immunometabolism and altered metabolic pathways as a means to understand the pathophysiology of aging and OA. Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant chondrocyte metabolism is a response to changes in the inflammatory microenvironment and may play a key role in cartilage degeneration and OA progression. Under conditions of environmental stress, chondrocytes tend to adapt their metabolism to microenvironmental changes by shifting from one metabolic pathway to another, for example from oxidative phosphorylation to glycolysis. Similar changes occur in other joint cells, including synoviocytes. Switching between these pathways is implicated in metabolic alterations that involve mitochondrial dysfunction, enhanced anaerobic glycolysis, and altered lipid and amino acid metabolism. The shift between oxidative phosphorylation and glycolysis is mainly regulated by the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways. Chondrocyte metabolic changes are likely to be a feature of different OA phenotypes. Determining the role of chondrocyte metabolism in OA has revealed key features of disease pathogenesis. Future research should place greater emphasis on immunometabolism and altered metabolic pathways as a means to understand the pathophysiology of age-related OA. This knowledge will advance the development of new drugs against therapeutic targets of metabolic significance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pioneered use of intra-articular injection of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) to treat osteoarthritis. • Applied a hybrid hydrogel incorporated with TPGS (TPGS@CS-hydrogel) to repair cartilage defect. • TPGS@CS-hydrogel resulted in excellent cartilage repair outcomes. • The chondrogenic capacity of mesenchymal stem cell improved in TPGS@CS-hydorgel. Osteoarthritis (OA) is a progressive and degenerative disease associated with articular cartilage injury. Current conservative or surgical treatments cannot effectively terminate the progress of OA, usually leading to total joint replacement at the end stage. Also, it is still challenging to treat cartilage defect for it demands a dual-pronged approach which simultaneously addresses both cartilage repair and the relief of osteochondral inflammation. In this study, we embarked on a pioneering exploration of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), an FDA-approved, water-soluble derivative of natural vitamin E. TPGS was found to effectively relieve inflammation both in vitro and in vivo. We further extended the application of TPGS by establishing an injectable collagen-chondroitin sulfate (CS) hydrogel incorporated with TPGS (TPGS@CS-hydrogel), and achieved excellent cartilage repair. RNA-seq showed that the anti-inflammatory effect of TPGS@CS-hydrogel were related to the interruption of interplay of oxidative stress and inflammation, thus promoting cartilage regeneration. In conclusion, both TPGS and TPGS@CS-hydrogel provided new insights for the prevention and treatment of articular inflammation and cartilage lesion. [ABSTRACT FROM AUTHOR]