LncRNA PART1 modulates chondrocyte proliferation, apoptosis, and extracellular matrix degradation in osteoarthritis via regulating miR-373-3p/SOX4 axis.

Abstract

Osteoarthritis (OA) is a common disease in articular cartilages. It has been reported that long non-coding RNAs (lncRNAs) play an important role in various pathological processes of OA. However, the role of PART1 in OA development is unclear. The expression levels of PART1 and miR-373-3p were detected in cartilage tissues and chondrocytes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was determined by flow cytometry and Western blot assay. The expression of extracellular matrix (ECM)-related proteins was examined by Western blot assay. Expression of SRY-related high-mobility group box 4 (SOX4) was measured by qRT-PCR or Western blot assay. The interactions among PART1, miR-373-3p, and SOX4 were predicted using starBase v2.0 database and confirmed by Dual-Luciferase reporter assay and RNA immunoprecipitation (RIP) assay. PART1 and SOX4 were up-regulated while miR-373-3p was down-regulated in OA cartilage tissues and chondrocytes. PART1 silencing hindered cell proliferation and ECM degradation, and triggered cell apoptosis in OA chondrocytes. PART1 modulated SOX4 expression by targeting miR-373-3p. Inhibition of miR-373-3p restored the regulation of cell proliferation, ECM degradation, and apoptosis induced by interfering PART1. Upregulation of SOX4 restored the effects on OA progression induced by inhibiting PART1. PART1 promoted OA progression by regulating miR-373-3p/SOX4 axis, providing an effective therapeutic target for osteoarthritis.