| First Author | Hu S | Year | 2019 |
| Journal | Exp Mol Med | Volume | 51 |
| Issue | 10 | Pages | 1-13 |
| PubMed ID | 31586040 | Mgi Jnum | J:293631 |
| Mgi Id | MGI:6453038 | Doi | 10.1038/s12276-019-0322-3 |
| Citation | Hu S, et al. (2019) MicroRNA-455-3p promotes TGF-beta signaling and inhibits osteoarthritis development by directly targeting PAK2. Exp Mol Med 51(10):1-13 |
| abstractText | MicroRNAs (miRNAs, miR) play a key role in the pathogenesis of osteoarthritis (OA). Few studies have examined the regulatory role of P21-activated kinases (PAKs), a family of serine/threonine kinases, in OA. The aim of this study was to determine whether miR-455-3p can regulate cartilage degeneration in OA by targeting PAK2. MiR-455-3p knockout mice showed significant degeneration of the knee cartilage. MiR-455-3p expression increased and PAK2 expression decreased in the late stage of human adipose-derived stem cell (hADSC) chondrogenesis and in chondrocytes affected by OA. Furthermore, in both miR-455-3p-overexpressing chondrocytes and PAK2-suppressing chondrocytes, cartilage-specific genes were upregulated, and hypertrophy-related genes were downregulated. A luciferase reporter assay confirmed that miR-455-3p regulates PAK2 expression by directly targeting the 3'-untranslated regions (3'UTRs) of PAK2 mRNA. IPA-3, a PAK inhibitor, inhibited cartilage degeneration due to OA. Moreover, suppressing PAK2 promoted R-Smad activation in the TGF/Smad signaling pathway in chondrocytes. Altogether, our results suggest that miR-455-3p promotes TGF-beta/Smad signaling in chondrocytes and inhibits cartilage degeneration by directly suppressing PAK2. These results thus indicate that miR-455-3p and PAK2 are novel potential therapeutic agents and targets, respectively, for the treatment of OA. |
