FGF19 promotes cartilage destruction in the progress of temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease characterized by the progressive deterioration of the condylar cartilage, compensatory remodeling of subchondral bone, and persistent synovial inflammation. The onset of TMJOA is accompanied by the activation of cytokines, which exacerbate the imbalance in joint homeostasis and accelerate the destruction and even irreversible degradation of joint structures. FGF19, as an important multifunctional fibroblast growth factor, has been reported to be substantially up-regulated in the cavity of osteoarthritis joint. However, its role in TMJOA progression remains unclear. In this study, we investigated its role in the condyle cartilage in TMJOA. We first established a mouse TMJOA model by unilateral anterior crossbite (UAC) and achieved overexpression of FGF19 by direct injection of adeno-associated virus carrying the Fgf19 gene. We found that FGF19 exacerbated the progressive deterioration of cartilage-subchondral bone unit in the progression of TMJOA. FGF19 accelerated the phenotypic transformation from mature cartilage to hypertrophic cartilage by reducing the expression of collagen type II (COL2A1) and aggrecan, enhancing the expression of collagen type X (COL10A1), matrix metallopeptidase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5), and exhibiting a fibrocartilage-associated change in the cartilage layer by increasing the expression of collagen type I alpha 1 and 2 (COL1A1 and COL1A2). Furthermore, FGF19 induces calcification progression of cartilage hypertrophic layer by up-regulating the expression of dentin matrix acidic phosphoprotein 1 (DMP1) via transcription factor osterix (OSX). These data provide evidence of the importance of FGF19 in the progression of TMJOA and show potential cues for interventions of cartilage disease.