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Downregulation of antidifferentiation noncoding RNA promotes chondrogenic differentiation and calcification of ligamentum flavum‐derived mesenchymal stem cells
Author(s) -
Zhang Qiang,
Wang Shenyu,
Sheng Yifei,
Zhao Shujie,
Jiang Yuqing,
Zhou Dong,
Yang Huilin
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27611
Subject(s) - mesenchymal stem cell , gene knockdown , chondrogenesis , downregulation and upregulation , microbiology and biotechnology , cellular differentiation , calcification , biology , cell culture , pathology , biochemistry , medicine , gene , genetics
Ligamentum flavum (LF)‐derived mesenchymal stem cells (MSCs) have been implicated in the pathogenesis of calcification of the ligamentum flavum (CLF) leading to the increased presence of chondrocyte‐like cells and calcium deposition in CLF; however, the mechanisms of LF‐MSCs in differentiation are not defined. In this study, we investigated the role of antidifferentiation noncoding RNA (ANCR) in the differentiation of LF‐MSCs. We found that ANCR was downregulated in human CLF tissues. In cultured LF‐MSCs, ANCR downregulation led to decreased cell proliferation but enhanced chondrogenic differentiation and calcification. In contract, ANCR overexpression increased cell proliferation but inhibited differentiation and calcification. Mechanistically, we detected a positive correlation between ANCR and enhancer of zeste homolog 2 (EZH2) in human CLF tissues. In cultured LF‐MSCs, ANCR knockdown decreased while ANCR overexpression increased EZH2 expression. In addition, physical association between ANCR and EZH2 was revealed by an RNA pull‐down assay. Functionally, EZH2 overexpression prevented chondrogenic differentiation and calcification enhanced by ANCR knockdown. These findings indicated that ANCR upregulates EZH2 expression and physically binds to EZH2 in LF‐MSCs to suppress chondrogenic differentiation and calcification. Therefore, downregulated ANCR contributes to increasing of chondrocyte‐like cells and calcium deposition in CLF. ANCR may serve as a therapeutic target for CLF.