FGF8 accelerates osteoarthritic chondrocyte hypertrophy by JunB-mediated cytokine perturbation.

Abstract

Temporomandibular joint osteoarthritis (TMJOA) is recognized as one of the most important oral-maxillofacial degenerative diseases, and affects a large group of the population worldwide. The progression of TMJOA is accompanied by an imbalance of cytokines in the joint cavity and a slow but long-lasting degradation of the joint tissues. FGF8, an important member of the fibroblast growth factor family, has been shown to be up-regulated in the cavities of osteoarthritis joints. However, its role in TMJOA progression remains unclear. Here, we established a mouse TMJOA model by using unilateral anterior crossbite (UAC), and investigated the role of FGF8 on the changes in condylar cartilage in the progress of TMJOA by using adeno-associated virus carrying FGF8 gene. We found that FGF8 accelerated the cartilage deterioration during TMJOA progression. FGF8 overexpression partially impaired the mature phenotype of chondrocytes by decreasing the expression of collagen type II (COL2A1) and aggrecan, and exacerbated chondrocyte hypertrophy by increasing the expression of collagen type X (COL10A1), matrix metallopeptidase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5). FGF8 promotes chondrocyte cytokine perturbation by up-regulating the expression profiles of inflammatory factors, chemotactic factors and interferons and down-regulating the expression of growth factors via the transcription factor JunB. Furthermore, FGF8-mediated JunB facilitates chondrocyte hypertrophy by binding to the promoters of Col10α1 and Mmp13. These results help understand the importance of FGF8 in the progression of TMJOA and provide cues for potential therapeutic strategies for osteoarthritis.