Adrenaline inhibits osteogenesis via repressing miR-21 expression.
Sympathetic signaling is involved in bone homeostasis; however, the cellular and molecular mechanisms remain unknown. In this study, we found that the psychological stress mediator adrenaline inhibited osteogenic differentiation of human bone marrow-derived stem cells (hMSC) by reducing microRNA-21 (miR-21) expression. Briefly, adrenaline significantly inhibited the osteogenic differentiation of hMSCs, as observed with both Alizarin red staining and maker gene expression (RUNX2, OSX, OCN, and OPN). During this process, miR-21 was suppressed by adrenaline via inhibition of histone acetylation, as verified by H3K9Ac chromatin immunoprecipitation (ChIP) assay. MiR-21 was confirmed to promote hMSC osteogenic differentiation, and overexpression of miR-21 reversed the impeditive effect of adrenaline on hMSC osteogenic differentiation. Our results demonstrate that down-regulation of miR-21 is responsible for the adrenaline-mediated inhibition of hMSC osteogenic differentiation. These findings indicate a regulation of bone metabolism by psychological stress and also provide a molecular basis for psychological stress-associated bone diseases.
Department of Dental Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Yanchang Road, Shanghai 200072, PR China.
Danying
D
Chen
Department of Dental Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Yanchang Road, Shanghai 200072, PR China.
Zuolin
Z
Wang
D000107:Acetylation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004837:Epinephrine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics
D006657:Histones; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D004837:Epinephrine
adrenaline; mesenchymal stem cells; miR-21; osteogenic differentiation; psychological stress