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

Yokota,Seiji; Chosa,Naoyuki; Kyakumoto,Seiko; Kimura,Hitomichi; Ibi,Miho; Kamo,Masaharu; Satoh,Kazuro; Ishisaki,Akira

doi:10.3892/ijmm.2017.2896

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

Authors:
- Seiji Yokota
- Naoyuki Chosa
- Seiko Kyakumoto
- Hitomichi Kimura
- Miho Ibi
- Masaharu Kamo
- Kazuro Satoh
- Akira Ishisaki
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Affiliations: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Iwate 028‑3694, Japan, Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University, Iwate 020‑8505, Japan
Published online on: February 17, 2017 https://doi.org/10.3892/ijmm.2017.2896
Pages: 799-808
Copyright: © Yokota et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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