Abstract
BACKGROUND Growing evidence suggests that long non-coding RNAs (lncRNAs), as decoys of microRNAs (miRNAs), are involved in osteoarthritis (OA) progression, but the potential mechanism of lncRNA SNHG15 in OA remains unknown. Thus, the present study explored the molecular mechanism of SNHG15 in OA progression. MATERIAL AND METHODS OA chondrocytes were created by 20 ng/ml IL-1ß stimulation, and the experimental OA model was created by destabilization of the medial meniscus (DMM) surgery. Cartilage histomorphology was observed by safranin and fast green double dyeing. The relationships between SNHG15 and miR-7, KLF4, and miR-7 were determined by dual-luciferase assay or RNA immunoprecipitation (RIP). Immunofluorescence was used to detect the expressions of Ki67, collagen II, and Aggrecan. Moreover, SNHG15, miR-7, KLF4, MMP3, ADAMTS5, COL2A1, Aggrecan, and ß-catenin expressions were assessed by qRT-PCR or Western blot. The methylation status of SNHG15 promoter was evaluated by MS-PCR. RESULTS Underexpression of KLF4 and SHNG15 and overexpression of miR-7 were found in human OA knee cartilage tissues and IL-1ß-stimulated OA chondrocytes. SHNG15 overexpression significantly inhibited ECM degradation and promoted chondrocyte formation of OA chondrocytes. Furthermore, SNHG15 regulated KLF4 expression by sponging miR-7. Further analysis found that SNHG15 significantly inhibited b-catenin in OA chondrocytes. SNHG15 had a higher level of methylation in human OA tissues than in normal cartilage tissues. CONCLUSIONS Our results revealed that SNHG15 alleviated OA progression by regulating ECM homeostasis, which provides a promising target for OA therapy.