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ROCK/actin/MRTF signaling promotes the fibrogenic phenotype of fibroblast-like synoviocytes derived from the temporomandibular joint.

Abstract：

:Malocclusion caused by abnormal jaw development or muscle overuse during mastication results in abnormal mechanical stress to the tissues surrounding the temporomandibular joint (TMJ). Excessive mechanical stress against soft and hard tissues around the TMJ is involved in the pathogenesis of inflammatory diseases, including osteoarthritis (OA). OA-related fibrosis is a possible cause of joint stiffness in OA. However, cellular and molecular mechanisms underlying fibrosis around the TMJ remain to be clarified. Here, we established a cell line of fibroblast‑like synoviocytes (FLSs) derived from the mouse TMJ. Then, we examined whether the Rho‑associated coiled‑coil forming kinase (ROCK)/actin/myocardin-related transcription factor (MRTF) gene regulatory axis positively regulates the myofibroblast (MF) differentiation status of FLSs. We found that i) FLSs extensively expressed the MF markers α‑smooth muscle actin (α‑SMA) and type I collagen; and ii) an inhibitor against the actin‑polymerizing agent ROCK, Y‑27632; iii) an actin-depolymerizing agent cytochalasin B; iv) an inhibitor of the MRTF/serum response factor‑regulated transcription, CCG‑100602, clearly suppressed the mRNA levels of α‑SMA and type I collagen in FLSs; and v) an MF differentiation attenuator fibroblast growth factor‑1 suppressed filamentous actin formation and clearly suppressed the mRNA levels of α-SMA and type I collagen in FLSs. These results strongly suggest that the ROCK/actin/MRTF axis promotes the fibrogenic activity of synoviocytes around the TMJ. Our findings partially clarify the molecular mechanisms underlying the emergence of TMJ‑OA and may aid in identifying drug targets for treating this condition at the molecular level.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Yokota S,Chosa N,Kyakumoto S,Kimura H,Ibi M,Kamo M,Satoh K,Ishisaki A

doi

10.3892/ijmm.2017.2896

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

799-808

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

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ROCK/actin/MRTF signaling promotes the fibrogenic phenotype of fibroblast-like synoviocytes derived from the temporomandibular joint.