Aims. Excessive chondrocyte hypertrophy is a common feature in cartilage degeneration which is susceptible to joint overloading, but the relationship between mechanical overloading and chondrocyte hypertrophy still remains elusive. The aim of our study was to explore the mechanism of mechanical compression-induced chondrocyte hypertrophy. Methods. In this study, the temporomandibular joint (TMJ) degeneration model was built through forced mandibular retrusion (FMR)-induced compression in TMJ. Chondrocytes were also mechanically compressed in vitro. The role of O-GlcNAcylation in mechanical compression-induced chondrocyte hypertrophy manifested through specific activator Thiamet G and inhibitor OSMI-1. Results. Both in vivo and in vitro data revealed that chondrocyte hypertrophic differentiation is promoted by compression. Immunofluorescent and immunoblotting results showed that protein pan-O-GlcNAcylation levels were elevated in these hypertrophic chondrocytes. Pharmacologically inhibiting protein pan-O-GlcNAcylation by OSMI-1 partially mitigated the compression-induced hypertrophic differentiation of chondrocytes. Specifically, runt-related transcription factor 2 (Runx2) and SRY-Box 9 transcription factor (Sox9) were subjected to modification of O-GlcNAcylation under mechanical compression, and pharmacological activation or inhibition of O-GlcNAcylation affected the transcriptional activity of Runx2 but not Sox9. Furthermore, compression-induced protein pan-O-GlcNAcylation in chondrocytes was induced by enhanced expression of glucose transporter 1 (GLUT1), and depletion of GLUT1 by WZB117 dampened the effect of compression on chondrocyte hypertrophy. Conclusion. Our study proposes a novel function of GLUT1-mediated protein O-GlcNAcylation in driving compression-induced hypertrophic differentiation of chondrocytes by O-GlcNAc modification of Runx2, which promoted its transcriptional activity and strengthened the expressions of downstream hypertrophic marker. Cite this article: Bone Joint Res 2025;14(3):209–222

Aims. Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear. Methods. Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis. Results. Abnormal adipogenesis, characterized by increased expression of CCAAT/enhancer-binding protein α (CEBPα), fatty acid binding protein 4 (FABP4), Perilipin1, Adiponectin (AdipoQ), and peroxisome proliferator-activated receptor γ (PPARγ), was enhanced in the degenerative cartilage of TMJ OA in UAC mice, accompanied by decreased expression of GDF11. After FFSS stimulation, there were fat droplets in the cytoplasm of cultured cells with increased expression of PPARγ, CEBPα, FABP4, Perilipin1, and AdipoQ and decreased expression of GDF11. Exogenous GDF11 inhibited increased lipid droplets and expression of AdipoQ, CEBPα, and FABP4 induced by FFSS stimulation. GDF11 did not affect the change in PPARγ expression under FFSS, but promoted its post-translational modification by small ubiquitin-related modifier (SUMOylation). Local injection of GDF11 alleviated TMJ OA-related cartilage degeneration and abnormal adipogenesis in UAC mice. Conclusion. Abnormal adipogenesis of chondrocytes and decreased GDF11 expression were observed in degenerative cartilage of TMJ OA. GDF11 supplementation effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration. GDF11 may inhibit the abnormal adipogenesis of chondrocytes by affecting the SUMOylation of PPARγ. Cite this article: Bone Joint Res 2022;11(7):453–464

Aims. In the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism. Methods. SMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated. Results. Interleukin (IL)-1β inhibited the chondrogenic differentiation potential of SMSCs, while the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and panobinostat (LBH589), attenuated inhibition of IL-1β-induced SMSC chondrogenesis. Additionally, SAHA attenuated the destruction of condylar cartilage in rat TMJ arthritis model. IL-6 (p < 0.001) and matrix metalloproteinase 13 (MMP13) (p = 0.006) were significantly upregulated after IL-1β stimulation, while SAHA and LBH589 attenuated IL-6 and MMP13 expression, which was upregulated by IL-1β in vitro. Silencing of IL-6 significantly downregulated MMP13 expression and attenuated IL-1β-induced chondrogenesis inhibition of SMSCs. Conclusion. HDAC inhibitors SAHA and LBH589 attenuated chondrogenesis inhibition of SMSC induced by IL-1β in TMJ, and inhibition of IL-6/MMP13 pathway activation contributes to this biological progress. This study provides a theoretical basis for the application of HDAC inhibitors in the treatment of TMJ arthritis. Cite this article: Bone Joint Res 2022;11(1):40–48

Aims

The aim of our study is to investigate the effect induced by alternated mechanical loading on Notch-1 in mandibular condylar cartilage (MCC) of growing rabbits.