Long non-coding RNA XIST promotes extracellular matrix degradation by functioning as a competing endogenous RNA of miR-1277-5p in osteoarthritis

Abstract

Osteoarthritis (OA) is a common and troublesome disease among the elderly, and is characterized by extracellular matrix (ECM) degradation. The function of the long non-coding RNA X-inactive-specific transcript (XIST) and its working mechanism in ECM degradation remains unclear. In the present study, XIST was revealed to be upregulated in OA specimens and in articular chondrocytes (ACs) derived from OA tissue (AC/OA) and interleukin-1β (IL-1β)-treated ACs. Loss-of-function experiments demonstrated that downregulation of XIST suppressed the degradation of the ECM in AC/OA and AC/IL-1β-5.0 cells. Furthermore, XIST, matrix metalloproteinase 13 (MMP-13) and ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) were identified as targets of microRNA (miR)-1277-5p, and the reciprocal inhibitive effect between XIST and miR-1277-5p was elucidated. Furthermore, the role of XIST in ECM degradation was confirmed to be functioning as a competing endogenous RNA (ceRNA) of miR-1277-5p. Finally, the protective effect of the downregulation of XIST on ECM degradation was verified in an OA rat model. In conclusion, the present study suggests that XIST promotes MMP-13 and ADAMTS5 expression, indicating ECM degradation, by functioning as a ceRNA of miR-1277-5p in OA. The present study proposed a novel potential target with a new working mechanism in molecular treating of OA.