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IL‐1β inhibits osteogenesis of human bone marrow‐derived mesenchymal stem cells by activating FoxD3/microRNA‐496 to repress wnt signaling
Author(s) -
Huang Jian,
Chen Liang
Publication year - 2017
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/dvg.23040
Subject(s) - wnt signaling pathway , mesenchymal stem cell , progenitor cell , microrna , microbiology and biotechnology , proinflammatory cytokine , biology , bone marrow , stem cell , cancer research , transcription factor , inflammation , signal transduction , immunology , gene , genetics
Summary IL‐1β, a major cytokine of proinflammatory response, has been implicated in bone loss. However, its effects on mesenchymal progenitor cells‐associated bone regeneration remain elusive. Here, we investigated the role of microRNA for the regulation of osteogenesis by IL‐1β in human bone marrow‐derived mesenchymal stem cells (hBMMSC). Our data suggested Homo sapiens (hsa)‐miR‐496 is induced by IL‐1β in hBMMSC and mediates the decreased β‐catenin expression. Reporter assays using the 3′‐UTR of β‐catenin demonstrated sequence‐dependent gene suppression with hsa‐miR‐496. IL‐1β activated hsa‐miR‐496 expression through a transcription factor, Foxhead box D3 protein (FoxD3). The activation of hsa‐miR‐496 promoter in hBMMSC depended on a consensus FoxD3 binding motif. Under osteogenic differentiation, IL‐1β treatment or overexpressing hsa‐miR‐496 attenuated bone mineralization and bone marker gene expressions in hBMMSC. Further, anti‐miR‐496 rescued the inhibitory effects of IL‐1β. Our findings suggest a pivotal role of hsa‐miR‐496 in linking inflammation to impaired bone regeneration, and provide a rationale for using appropriate hsa‐miR‐496 inhibitors in the treatment of inflammation‐associated bone loss.