HMGB1 is a bone‐active cytokine

Journal of Cellular Physiology - Tập 214 Số 3 - Trang 730-739 - 2008
Jieping Yang1, Rita Shah2, Alexander G. Robling2, Evan Templeton2, Huan Yang3, Kevin J. Tracey3, Joseph P. Bidwell2
1Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
2Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana
3Laboratory of Biomedical Sciences, Institute for Medical Research, North Shore‐Long Island Jewish Health System, Manhasset, New York

Tóm tắt

Abstract

High mobilitygroupbox 1 (HMGB1) is a chromatin protein that acts as an immunomodulatory cytokine upon active release from myeloid cells. HMGB1 is also an alarmin, an endogenous molecule released by dying cells that acts to initiate tissue repair. We have previously reported that osteoclasts and osteoblasts release HMGB1 and release by the latter is regulated by parathyroid hormone (PTH), an agent of bone remodeling. A recent study suggests that HMGB1 acts as a chemotactic agent to osteoclasts and osteoblasts during endochondral ossification. To explore the potential impact of HMGB1 in the bone microenvironment and its mechanism of release by osseous cells, we characterized the effects of recombinant protein (rHMGB1) on multiple murine bone cell preparations that together exhibit the various cell phenotypes present in bone. We also inquired whether apoptotic bone cells release HMGB1. rHMGB1 enhanced the RANKL/OPG steady state mRNA ratio and dramatically augmented the release of tumor necrosis factor‐alpha (TNFα) and interleukin‐6 (IL6) in osteoblastogenic bone marrow stromal cell (BMSC) cultures but not in the calvarial‐derived MC3T3‐E1 cells. Interestingly, rHMGB1 promoted GSK‐3beta phosphorylation in MC3T3‐E1 cells but not in BMSCs. Apoptotic bone cells released HMGB1, including MLO‐Y4 osteocyte‐like cells. MLO‐Y4 release of HMGB1 was coincident with caspase‐3 cleavage. Furthermore, the anti‐apoptotic action of PTH on MC3T3‐E1 cells correlated with the observed decrease in HMGB1 release. Our data suggest that apoptotic bone cells release HMGB1, that within the marrow HMGB1 is a bone resorption signal, and that intramembraneous and endochondral osteoblasts exhibit differential responses to this cytokine. J. Cell. Physiol. 214: 730–739, 2008. © 2007 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1084/jem.192.4.565

10.1152/ajpcell.00616.2005

10.1074/jbc.M307444200

10.1210/en.2003-0319

10.1016/j.tcb.2004.04.004

10.1189/jlb.0306164

10.1093/emboj/cdg516

Bonewald LF, 2002, Osteocytes: A proposed multifunctional bone cell, J Musculoskelet Neuronal Interact, 2, 239

Breuil V, 2003, The receptor activator of nuclear factor (NF)‐kappaB ligand (RANKL) is a new chemotactic factor for human monocytes, FASEB J, 17, 1751, 10.1096/fj.02-1188fje

10.1002/jcp.20577

10.1074/jbc.M108913200

10.1182/blood-2004-02-0474

10.1016/j.bone.2005.10.007

10.1083/jcb.152.6.1197

10.1016/j.molimm.2004.07.023

10.1016/j.bbrc.2005.12.107

Dovio A, 2005, Circulating osteoprotegerin and soluble RANKL: Do they have a future in clinical practice?, J Endocrinol Invest, 28, 14

10.4049/jimmunol.174.12.7506

10.1210/en.2003-0726

10.1016/j.cca.2006.03.017

10.1359/JBMR.0301226

10.4049/jimmunol.170.7.3688

10.4049/jimmunol.166.5.3574

10.1002/art.11161

10.1016/j.cytogfr.2003.10.005

10.1016/j.jim.2004.04.019

10.1038/nri1594

10.4049/jimmunol.176.1.12

10.1080/09243860500096248

10.1074/jbc.M510160200

10.1152/ajpcell.00322.2002

10.1038/emm.2005.65

10.1084/jem.20052203

Rho J, 2004, Osteoimmunology: Interactions of the immune and skeletal systems, Mol Cells, 17, 1, 10.1016/S1016-8478(23)12997-9

10.1074/jbc.M509436200

10.1182/blood-2003-10-3536

10.1038/sj.embor.7400205

10.1074/jbc.M107627200

10.3748/wjg.v12.i47.7666

10.1038/nature00858

10.1111/j.1582-4934.2005.tb00337.x

10.1016/j.clim.2003.09.001

10.1111/j.1600-0765.2005.00814.x

10.1038/nri2062

10.1128/MCB.00130-07

10.1158/0008-5472.CAN-06-0743

10.1016/j.molmed.2005.11.007

10.1146/annurev.immunol.24.021605.090646

10.1126/science.285.5425.248

10.1359/jbmr.1999.14.6.893

10.1152/ajpendo.00216.2006

10.1007/s11914-005-0016-8

10.1016/j.bbcan.2004.05.002

10.1016/j.ceb.2005.02.010

10.1016/j.mehy.2005.07.017

10.1006/bbrc.1999.0871

10.2119/2006-00010.Yang

10.1097/01.shk.0000225404.51320.82

10.4049/jimmunol.166.3.1482

10.1097/00002371-200501000-00001

10.1084/jem.20051947

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Journal of Cellular Physiology

Tập 214 Số 3

730-739

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