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


ABSTRACT: 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 ?B (NF-?B) signaling pathway, a downstream pathway of MAP3K7, was also repressed by miR-10a in OA-FLSs. To summarize, the TWIST1-miR-10a-MAP3K7-NF-?B pathway mediates the development of synovitis in OA. miR-10a functions as an anti-inflammatory mediator in OA-FLS.

SUBMITTER: Tu J 

PROVIDER: S-EPMC7691159 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Tu Jiajie J   Huang Wei W   Zhang Weiwei W   Mei Jiawei J   Yu Zhiying Z   Zhu Chen C  

Molecular therapy. Nucleic acids 20201022


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, m  ...[more]

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