Receptor tyrosine kinase ligands and inflammatory cytokines cooperatively suppress the fibrogenic activity in temporomandibular‑joint‑derived fibroblast‑like synoviocytes via mitogen‑activated protein kinase kinase/extracellular signal‑regulated kinase

Abstract

Osteoarthritis (OA)-related fibrosis is a possible cause of temporomandibular joint (TMJ) stiffness. However, the molecular mechanisms underlying the fibrogenic activity in fibroblast‑like synoviocytes (FLSs) remain to be clarified. The present study examined the effects of receptor tyrosine kinase (RTK) ligands, such as fibroblast growth factor (FGF)‑1 and epidermal growth factor (EGF), on myofibroblastic differentiation of the FLS cell line FLS1, which is derived from the mouse TMJ. The present study revealed that both FGF‑1 and EGF dose‑dependently suppressed the expression of the myofibroblast (MF) markers, including α‑smooth muscle actin (α‑SMA) and type I collagen, in FLS1 cells. Additionally, both FGF‑1 and EGF activated extracellular signal‑regulated kinase (ERK) in FLS1 cells. In addition, the mitogen‑activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor U0126 abrogated the FGF‑1‑ and EGF‑mediated suppression of MF marker expression. On the other hand, inflammatory cytokines, such as interleukin‑1β and tumor necrosis factor‑α, also suppressed the expression of MF markers in FLS1 cells. Importantly, U0126 abrogated the inflammatory cytokine‑mediated suppression of MF marker expression. Interestingly, RTK ligands and inflammatory cytokines additively suppressed the expression of type I collagen. These results suggested that RTK ligands and inflammatory cytokines cooperatively inhibited the fibrogenic activity in FLSs derived from the TMJ in a MEK/ERK‑dependent manner. The present findings partially clarify the molecular mechanisms underlying the development of OA‑related fibrosis in the TMJ and may aid in identifying therapeutic targets for this condition. Additionally, FGF‑1 and EGF could be therapeutically utilized to prevent OA‑related fibrosis around the inflammatory TMJ.