LncRNA CTBP1-AS2 is upregulated in osteoarthritis and increases the methylation of miR-130a gene to inhibit chondrocyte
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ORIGINAL ARTICLE
LncRNA CTBP1-AS2 is upregulated in osteoarthritis and increases the methylation of miR-130a gene to inhibit chondrocyte proliferation Hongfei Zhang 1 & Jinglian Li 2 & Weiguang Shao 1 & Naipeng Shen 1 Received: 6 November 2019 / Revised: 24 March 2020 / Accepted: 16 April 2020 # International League of Associations for Rheumatology (ILAR) 2020
Abstract Objectives LncRNA CTBP1-AS2 has been reported to be involved in type 2 diabetes and cardiomyocyte hypertrophy, while its roles in other human diseases are unknown. Our preliminary deep sequencing analysis showed altered expression of CTBP1-AS2 in osteoarthritis (OA). In addition, CTBP1-AS2 was inversely correlated with miR-130a. This study was therefore carried out to investigate the interactions between CTBP1-AS2 and miR-130a in OA. Methods Synovial fluid was collected from 62 OA patients and 62 healthy controls. RT-qPCR was performed to determine the expression levels of CTBP1-AS2 and miR-130a in synovial fluid. Cell transfections were performed to investigate the interactions between CTBP1-AS2 and miR-130a. Methylation-specific PCR (MSP) was performed to assess the effects of CTBP1-AS2 on the methylation of miR-130a. Cell counting Kit-8 (CCK-8) assay was performed to evaluate the roles of CTBP1-AS2 and miR-130a in regulating proliferation of chondrocytes. Results The results showed that CTBP1-AS2 was upregulated in OA and inversely correlated with miR-130a. In chondrocytes of OA patients, overexpression of CTBP1-AS2 led to increased methylation of miR-130a gene and downregulated expression of miR-130a, while overexpression of miR-130a did not affect the expression of CTBP1AS2. In contrast, no interaction between CTBP1-AS2 and miR-130a was observed in chondrocytes from healthy adults. Analysis of chondrocyte proliferation showed that overexpression of miR-130a led to increased proliferation rate of chondrocytes extracted from OA patients. Overexpression of CTBP1-AS2 led to decreased proliferation rate of chondrocytes and reversed the effects of overexpressing miR-130a. Conclusion Therefore, CTBP1-AS2 is upregulated in OA and may increase the methylation of miR-130a gene to inhibit chondrocyte proliferation. Key Points • CTBP1-AS2 is overexpressed in OA and may downregulate miR-130a through methylation to suppress the proliferation of chondrocytes. • The interaction between CTBP1-AS2 and miR-130a is indirect and mediated by certain pathological mediators.
Keywords Chondrocyte . CTBP1-AS2 . miR-130a . Osteoarthritis . Proliferation
Introduction * Weiguang Shao [email protected] * Naipeng Shen [email protected] 1
Department of Arthritis, Affiliated Hospital of Weifang Medical University, No. 2428, Yuhe Road, Kuiwen District, Weifang City 261031, Shandong Province, China
2
Weifang Medical University, NO.4948 Shengli East Street, Weifang City, 261042, Shandong Province, China
Osteoarthritis (OA) as the major subtype of arthritis that affects millions of people worldwide is caused by the damages of protective cartilage at the ends of bones in a jo
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