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 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 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 ,, and 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.

Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders

“…To verify the reliability of these methods, other types of TMD models are also needed, including mechanical stimulus-induced models, in which specific appliances have been employed to develop abnormal occlusal conditions, 39 , 40 the noxious stimulus model by orofacial formalin injection, 41 the TMJ inflammation mouse model, which is induced by the injection of complete Freund’s adjuvant, 42 , 43 and genetic mouse models. 13 , 44 Moreover, these methods should be further optimised in future experiments.…”

Automated Indentation Demonstrates Structural Stiffness of Femoral Articular Cartilage and Temporomandibular Joint Mandibular Condylar Cartilage Is Altered in FgF2KO Mice

“…The results in this study also demonstrate, for the first time, the effect of FGF2 expression on structural stiffness of the TMJ MCC. While the effects of FgFr1 and FgFr3 on murine osteoarthritis in the TMJ have been studied, 19,20 to the authors’ best knowledge, this is the first study to employ automated indentation testing on the small murine TMJ and demonstrate a role of FGF2 in MCC homeostasis. FGF2 can therefore be added to the list of other matrix molecules, including proteoglycan-4, 21,22 biglycan and fibromodulin, 23 collagen types II 24 and XI, 25 previously shown to play a role in TMJ homeostasis.…”

Autophagy Activation Is Involved in Acidic Fibroblast Growth Factor Ameliorating Parkinson’s Disease via Regulating Tribbles Homologue 3

“…After administration, it promotes the transfer of FGFR1 to the membrane, thereby promotes the repair of neuronal damage. In contrast, studies have shown that inhibition of the FGFR1 signaling pathway in the pathogenesis of temporomandibular joint osteoarthritis activates autophagy level, thereby ameliorates disease (Wang et al, 2018), probably due to FGFR1 having the different effects on different tissue.…”