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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890221 | PMC |
| http://dx.doi.org/10.1302/2046-3758.143.BJR-2024-0257.R1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanical compression induces chondrocyte hypertrophy by regulating Runx2 O-GlcNAcylation during temporomandibular joint condyle degeneration.
Bone Joint Res
March 2025
Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China.
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.
An "EVs-in-ECM" mimicking system orchestrates transcription and translation of RUNX1 for in-situ cartilage regeneration.
Mater Today Bio
April 2025
Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215006, China.
The self-repair ability of articular cartilage is limited, which is one of the most difficult diseases to treat clinically. Kartogenin (KGN) induces chondrogenesis by regulating RUNX1 mRNA translation and the small molecule compound TD-198946 (TD) promotes chondrogenic differentiation of mesenchymal stem cells (MSCs) through increasing the transcription of RUNX1 mRNA. GelMA hydrogel and liposomes are respectively similar to the extracellular matrix (ECM) and extracellular vesicles (EVs).
View Article and Find Full Text PDFIn cartilage tissue engineering, active TGF-β is conventionally supplemented in culture medium at highly supraphysiologic doses to accelerate neocartilage development. While this approach enhances cartilage extracellular matrix (ECM) biosynthesis, it further promotes tissue features detrimental to hyaline cartilage function, including the induction of tissue swelling, hyperplasia, hypertrophy, and ECM heterogeneities. In contrast, during native cartilage development, chondrocytes are surrounded by TGF-β configured in a latent complex (LTGF-β), which undergoes cell-mediated activation, giving rise to moderated, physiologic dosing regimens that enhance ECM biosynthesis while avoiding detrimental features associated with TGF-β excesses.
View Article and Find Full Text PDFInhibition of KDM6B prevents osteoarthritis by blocking growth plate-like H3K27me3 loss in bivalent genes.
Sci China Life Sci
February 2025
Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Osteoarthritis (OA) is the most prevalent joint disorder occurring with articular cartilage degradation. It includes a switch from an articular to a growth plate chondrocyte phenotype. Here, we investigated the histone modification profiles and found significant H3K27me3 loss in OA, which led to disease-associated gene expression.
View Article and Find Full Text PDFNuclear Factor of Activated T Cells Signalling and Viral Pathogens: A Dynamic Cross-Talk.
Rev Med Virol
March 2025
Hepatitis Research Center, Deputy of Research, Lorestan University of Medical Sciences, Khorramabad, Iran.
The signalling pathway of the nuclear factor of activated T cells (NFAT) plays a crucial role in regulating various cellular processes such as cardiac hypertrophy, adipose differentiation, chondrocyte development, angiogenesis, inflammation, immune system activation, organogenesis, cancer cell migration, differentiation and survival. In addition, the NFAT signalling pathway acts as a key regulator of viral infections. Accordingly, it is plausible to assume that viruses have developed different mechanisms to manipulate this pathway to promote their pathogenicity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!