IL-1β inhibits osteogenesis of human bone marrow-derived mesenchymal stem cells by activating FoxD3/microRNA-496 to repress wnt signaling

Genesis : the Journal of Genetics and Development
Jian Huang, Liang Chen

Abstract

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.

References

Sep 18, 1997·The Laryngoscope·R B MitchellR H Lazar
Mar 22, 2005·The Journal of Biological Chemistry·Xiaofeng LiDianqing Wu
Apr 5, 2008·Nature Protocols·Chang-Gong LiuCarlo M Croce
Jun 25, 2008·Journal of Prosthodontics : Official Journal of the American College of Prosthodontists·Annalisa PalmieriFrancesco Carinci
Dec 9, 2009·Current Osteoporosis Reports·Robert R McLean
Jan 12, 2010·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Bogusław CzernyAndrzej Pawlik
Mar 9, 2010·International Journal of Oral and Maxillofacial Surgery·A B PetkovićR J Kozomara
Aug 4, 2010·International Immunology·Young-Mi LeeYoichiro Iwakura
Sep 23, 2010·Annals of the Rheumatic Diseases·Gisela Ruiz HeilandJochen Zwerina
May 3, 2011·Current Genomics·Leigh-Ann Macfarlane, Paul R Murphy
Jun 26, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lige SongJun Guo
Oct 18, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nan YangYan Jin
Jul 19, 2014·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Mengmeng LiZhangbin Yu
Apr 8, 2015·Journal of Internal Medicine·U H Lerner, C Ohlsson
Nov 27, 2015·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Jun LiXijing He
Mar 24, 2016·Nature Communications·Mikaël M MartinoShizuo Akira
Apr 21, 2016·Cell Cycle·Claudia RubieMatthias Glanemann
Nov 22, 2016·Stem Cell Investigation·Jennifer L Plank-Bazinet, Nathan A Mundell

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Citations

Nov 5, 2019·Journal of Cellular Biochemistry·Yuzhuo WangMin Hu
Feb 19, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Mingzheng LiHuipin Yuan
Feb 6, 2020·Experimental and Therapeutic Medicine·Jing YeJie Tong
Aug 28, 2020·European Journal of Immunology·Alexander HackelSven Brandau
Jun 27, 2018·Scientific Reports·Ehsan Pashay Ahi, Kristina M Sefc
May 10, 2019·Journal of Cellular Biochemistry·Tayebe Moghaddam, Zeinab Neshati
Jul 9, 2018·ACS Biomaterials Science & Engineering·Runheng LiuZetao Chen

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