RRC ID 65545
著者 Yokota S, Chosa N, Kyakumoto S, Kimura H, Ibi M, Kamo M, Satoh K, Ishisaki A.
タイトル ROCK/actin/MRTF signaling promotes the fibrogenic phenotype of fibroblast-like synoviocytes derived from the temporomandibular joint.
ジャーナル Int J Mol Med
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.
巻・号 39(4)
ページ 799-808
公開日 2017-4-1
DOI 10.3892/ijmm.2017.2896
PMID 28259960
PMC PMC5360431
MeSH Actins / metabolism* Animals Female Malocclusion / metabolism Malocclusion / pathology Mice Osteoarthritis / metabolism* Osteoarthritis / pathology Signal Transduction* Stress, Mechanical Synoviocytes / metabolism* Synoviocytes / pathology Temporomandibular Joint / metabolism* Temporomandibular Joint / pathology Trans-Activators / metabolism* rho-Associated Kinases
IF 3.098
リソース情報
ヒト・動物細胞 RAW 264(RCB0535) NIH3T3