Abstract:
: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.
journal_name
J Cell Biochemjournal_title
Journal of cellular biochemistryauthors
Zhang Q,Wang S,Sheng Y,Zhao S,Jiang Y,Zhou D,Yang Hdoi
10.1002/jcb.27611subject
Has Abstractpub_date
2019-03-01 00:00:00pages
3401-3414issue
3eissn
0730-2312issn
1097-4644journal_volume
120pub_type
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