Molecular Therapy: Nucleic Acids (Dec 2020)

TWIST1-MicroRNA-10a-MAP3K7 Axis Ameliorates Synovitis of Osteoarthritis in Fibroblast-like Synoviocytes

  • Jiajie Tu,
  • Wei Huang,
  • Weiwei Zhang,
  • Jiawei Mei,
  • Zhiying Yu,
  • Chen Zhu

Journal volume & issue
Vol. 22
pp. 1107 – 1120

Abstract

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Synovitis refers to the inflammation of the synovial membrane and is commonly detected in patients with osteoarthritis (OA). Recent reports have suggested that microRNAs (miRNAs) could be a promising target for diagnosis and prognosis in OA. This study examines the effect of microRNA-10a (miR-10a) in fibroblast-like synoviocyte (FLS)-mediated synovitis obtained from patients with OA. Expression of miR-10a is negatively associated with the severity of synovitis. miR-10a inhibited proliferation, migration, and secretion of pro-inflammatory cytokines of OA-FLS that were obtained from OA patients in vitro. By using a patient-derived xenograft (PDX) model, miR-10a repressed proliferation of OA-FLSs and production of OA synovium-derived pro-inflammatory cytokines in vivo. Twist Family BHLH Transcription Factor 1 (TWIST1) and mitogen-activated protein kinase kinase kinase 7 (MAP3K7) were identified as an upstream regulator and direct target of miR-10a in OA-FLSs, respectively. Nuclear factor κB (NF-κB) signaling pathway, a downstream pathway of MAP3K7, was also repressed by miR-10a in OA-FLSs. To summarize, the TWIST1-miR-10a-MAP3K7-NF-κB pathway mediates the development of synovitis in OA. miR-10a functions as an anti-inflammatory mediator in OA-FLS.

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