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LncRNA CTBP1-AS2 is upregulated in osteoarthritis and increases the methylation of miR-130a gene to inhibit chondrocyte proliferation

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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 CTBP1-AS2. 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.

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Authors and Affiliations

  1. Department of Arthritis, Affiliated Hospital of Weifang Medical University, No. 2428, Yuhe Road, Kuiwen District, Weifang City, 261031, Shandong Province, China

    Hongfei Zhang, Weiguang Shao & Naipeng Shen

  2. Weifang Medical University, NO.4948 Shengli East Street, Weifang City,, 261042, Shandong Province, China

    Jinglian Li

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  1. Hongfei Zhang
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  2. Jinglian Li
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  3. Weiguang Shao
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Contributions

WGS and NPS: study concepts, study design, literature research, experimental studies, manuscript preparation and editing; HFZ: definition of intellectual content, literature research experimental studies, manuscript preparation and editing; JLL: literature research, experiments work and manuscript writing. All the authors read and approved the final manuscript.

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Correspondence to Weiguang Shao or Naipeng Shen.

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The authors declare that they have no competing interests.

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Ethical approval was obtained from the Ethics Committee of Affiliated Hospital of Weifang Medical University. Written informed consent was obtained from all individual patients included in the study.

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Zhang, H., Li, J., Shao, W. et al. LncRNA CTBP1-AS2 is upregulated in osteoarthritis and increases the methylation of miR-130a gene to inhibit chondrocyte proliferation. Clin Rheumatol 39, 3473–3478 (2020). https://doi.org/10.1007/s10067-020-05113-4

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  • DOI: https://doi.org/10.1007/s10067-020-05113-4

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