MicroRNA-455-3p promotes TGF-β signaling and inhibits osteoarthritis development by directly targeting PAK2

• DOI: 10.1038/s12276-019-0322-3
• Publication Date: 2019-10-04T09:05:14Z
• Authors: Shu Hu; Xiaoyi Zhao; Guping Mao; Ziji Zhang; Xingzhao Wen; Chengyun Zhang; Weiming Liao; Zhiqi Zhang
• Keywords: Chondrogenesis

Abstract MicroRNAs (miRNAs, miR) play a key role in the pathogenesis of osteoarthritis (OA). Few studies have examined regulatory P21-activated kinases (PAKs), family serine/threonine kinases, OA. The aim this study was to determine whether miR-455-3p can regulate cartilage degeneration OA by targeting PAK2. MiR-455-3p knockout mice showed significant knee cartilage. expression increased and PAK2 decreased late stage human adipose-derived stem cell (hADSC) chondrogenesis chondrocytes affected Furthermore, both miR-455-3p-overexpressing PAK2-suppressing chondrocytes, cartilage-specific genes were upregulated, hypertrophy-related downregulated. A luciferase reporter assay confirmed that regulates directly 3′-untranslated regions (3′UTRs) mRNA. IPA-3, PAK inhibitor, inhibited due Moreover, suppressing promoted R-Smad activation TGF/Smad signaling pathway chondrocytes. Altogether, our results suggest promotes TGF-β/Smad inhibits These thus indicate are novel potential therapeutic agents targets, respectively, for treatment