LncRNA PMS2L2 protects ATDC5 chondrocytes against lipopolysaccharide-induced inflammatory injury by sponging miR-203.

PMS1 Homolog 2, Mismatch Repair System Component Pseudogene 2 (PMS2L2) has been reported as an up-regulated long non-coding RNA (lncRNA) in osteoarthritis (OA) tissues. The purpose of the present work is to explore whether the differently expressed PMS2L2 is associated with the pathogenesis of OA. Chondrogenic ATDC5 cells were exposed to various doses of lipopolysaccharide (LPS). The expression of PMS2L2, miR-203, and MCL-1 in cell was altered by transfection. Thereafter, cell viability, apoptosis, the expression changes of apoptosis-related factors and the release of pro-inflammatory factors were respectively assessed. Moreover, the regulatory relationship between PMS2L2 and miR-203, as well as between miR-203 and MCL-1 were studied. PMS2L2 expression was down-regulated following LPS stimulation. PMS2L2 protected ATDC5 cells against LPS-induced injury by increasing cell viability, decreasing apoptosis, and repressing the release of pro-inflammatory factors. Meanwhile, PMS2L2 increased the expression levels of COL2A1 and ACAN, while down-regulated the expression levels of MMP13 and ADAMTS-5. PMS2L2 worked as a molecular sponge for miR-203. Besides, miR-203 overexpression partially abolished the chondroprotective effects of PMS2L2. MCL-1 was a direct target of miR-203, and it exerted the similarly chondroprotective effects as PMS2L2. Furthermore, PMS2L2 and MCL-1 blocked Wnt/β-Catenin and JAK/STAT signaling pathways also via a miR-203-dependent manner. Our study reveals a protective role of PMS2L2 in LPS-induced inflammatory injury in chondrocytes. PMS2L2/miR-203/MCL-1 axis may serve as a new gene therapy strategy for the treatment of OA.