Journal
LIFE SCIENCES
Volume 217, Issue -, Pages 283-292Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.12.020
Keywords
lncRNA; PMS2L2; miR-203; MCL-1; Lipopolysaccharide (LPS); Osteoarthritis
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Aims: 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. Main methods: 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. Key findings: 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/beta-Catenin and JAK/STAT signaling pathways also via a miR-203-dependent manner. Significance: 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.
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