Long Non-coding XIST Raises Methylation of TIMP-3 Promoter to Regulate Collagen Degradation in Osteoarthritic Chondrocytes After Tibial Plateau Fracture

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2019 Dec 10

PMID 31815654

Citations 20

Authors

Hongwei Chen

Shengdi Yang

Ruyi Shao

Affiliations

Soon will be listed here.

Abstract

Background: Hypermethylation of gene promoters has been regarded as an epigenetic regulator for gene inactivation in the development of several diseases. In the current study, we aimed to explore how long noncoding RNA X-inactive specific transcript (lncRNA XIST) function in collagen degradation in chondrocytes of osteoarthritis (OA) after tibial plateau fracture by regulating tissue inhibitor of metalloproteinase-3 (TIMP-3) promoter methylation.

Methods: In silico analysis was used to screen differentially expressed lncRNAs in cartilage tissues of OA. Chondrocytes were then successfully isolated from normal and OA cartilage tissues and identified, with the expressions of lncRNA XIST and TIMP-3 examined. The methylation levels of TIMP-3 promoter were determined by MS-PCR. The binding of lncRNA XIST to DNA methyltransferase and the binding of TIMP-3 promoter to DNA methyltransferase were determined by a series of experiments, including RIP, RNA pull-down, and ChIP assays.

Results: The differentially expressed lncRNA XIST was determined in OA. In addition, cartilage tissues of OA showed upregulation of lncRNA XIST and downregulation of TIMP-3. LncRNA XIST was primarily localized in the nucleus and was capable of binding to the promoter of TIMP-3. The silencing of lncRNA XIST decreased the methylation levels of TIMP-3 promoter and increased the expressions of TIMP-3, which consequently inhibited collagen degradation in OA chondrocytes. Furthermore, TIMP-3 over-expression reversed the effect of lncRNA XIST on collagen degradation in OA chondrocytes.

Conclusion: Collectively, lncRNA XIST raises collagen degradation in OA chondrocytes after tibial plateau fracture by accelerating the methylation of TIMP-3 promoter by recruiting DNA methyltransferase.

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