miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2

• DOI: 10.1038/cddis.2017.146
• Publication Date: 2017-04-06T16:40:50Z
• Authors: Xudong Zhang; Chuandong Wang; Jingyu Zhao; Jiajia Xu; Yiyun Geng; Liming Dai; Yan Huang; Sai-Chuen Fu; Kerong Dai; Xiaoling Zhang
• Keywords: Homeostasis; Knockout mouse

Abstract Osteoarthritis (OA), characterized by insufficient extracellular matrix synthesis and cartilage degeneration, is known as an incurable disease because its pathogenesis poorly elucidated. Thus far, limited information available regarding the pathophysiological role of microRNAs (miRNAs) in OA. In this study, we investigated specific function miR-146a OA pathophysiology using mouse models. We found that articular degeneration knockout (KO) mice was alleviated compared with wild-type (WT) spontaneous instability-induced demonstrate aggravated pro-inflammatory cytokines induced suppressing expression matrix-associated genes. further identified calcium/calmodulin-dependent protein kinase II delta (Camk2d) phosphatase 3, regulatory subunit B, beta isoform (Ppp3r2, also calcineurin type II) were essential targets regulating homeostasis. Moreover, surgical-induced treated a inhibitor significantly destruction via targeting Camk2d Ppp3r2. These results suggested has crucial maintaining MiR-146a inhibition chondrocytes can be potential therapeutic strategy to ameliorate