Loss of Fgfr1 in chondrocytes inhibits osteoarthritis by promoting autophagic activity in temporomandibular joint

Abstract

Temporomandibular joint osteoarthritis (TMJ OA) is a common degenerative disease with few effective disease-modifying treatments in the clinic. Fibroblast growth factor (FGF) signaling is implicated in articular cartilage homeostasis, but the functional roles of FGFR1 in TMJ OA remain largely unknown. In this study, we report that deletion of <i>Fgfr1</i> in TMJ chondrocytes delayed TMJ OA progression in the age-associated spontaneous OA model and the abnormal dental occlusion OA model. Immunohistochemical staining revealed that <i>Fgfr1</i> deficiency decreased the expressions of MMP13 (matrix metalloproteinase-13), ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5), and COL10A1 but increased aggrecan expression level in two TMJ OA models. Furthermore, our data show that inactivation of FGFR1 signaling may promote autophagic activity in TMJ. FGFR1 inhibitor decreased the expressions of <i>Mmp13</i>, <i>Adamts5</i>, and <i>Runx2</i> in IL-1β-stimulated condylar chondrocytes, whereas autophagy inhibitors abrogated the protective effects of the FGFR1 inhibitor. Thus, our study indicates inactivated FGFR1 signaling ameliorates TMJ OA progression partially by promoting autophagic activity. Manipulation of this signaling may be a potential therapeutic approach to modify TMJ OA.