Tributyltin induces distinct effects on cortical and trabecular bone in female C57Bl/6J mice

Journal of Cellular Physiology - Tập 233 Số 9 - Trang 7007-7021 - 2018
James Watt1, Amelia H. Baker2, Brett Meeks3, Paola Divieti Pajevic4, Elise F. Morgan5,3, Louis C. Gerstenfeld3, Jennifer J. Schlezinger1
1Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts
2Department of Medicine, Boston University School of Medicine; Boston, Massachusetts
3Department of Orthopaedic Surgery, Boston University School of Medicine, Boston, Massachusetts;
4Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, Massachusetts
5Department of Mechanical Engineering, Boston University, Boston, Massachusetts

Tóm tắt

The retinoid X receptors (RXR), peroxisome proliferator activated receptor gamma (PPARγ), and liver X receptors (LXR) all have been shown to regulate bone homeostasis. Tributyltin (TBT) is an environmental contaminant that is a dual RXRα/β and PPARγ agonist. TBT induces RXR, PPARγ, and LXR‐mediated gene transcription and suppresses osteoblast differentiation in vitro. Bone marrow multipotent mesenchymal stromal cells derived from female C57BL/6J mice were more sensitive to suppression of osteogenesis by TBT than those derived from male mice. In vivo, oral gavage of 12 week old female, C57Bl/6J mice with 10 mg/kg TBT for 10 weeks resulted in femurs with a smaller cross‐sectional area and thinner cortex. Surprisingly, TBT induced significant increases in trabecular thickness, number, and bone volume fraction. TBT treatment did not change the Rankl:Opg RNA ratio in whole bone, and histological analyses showed that osteoclasts in the trabecular space were minimally reduced. In contrast, expression of cardiotrophin‐1, an osteoblastogenic cytokine secreted by osteoclasts, increased. In primary bone marrow macrophage cultures, TBT marginally inhibited the number of osteoclasts that differentiated, in spite of significantly suppressing expression of osteoclast markers Nfatc1, Acp5, and Ctsk and resorptive activity. TBT induced expression of RXR‐ and LXR‐dependent genes in whole bone and in vitro osteoclast cultures. However, only an RXR antagonist, but not an LXR antagonist, significantly inhibited TBTs ability to suppress osteoclast differentiation. These results suggest that TBT has distinct effects on cortical versus trabecular bone, likely resulting from independent effects on osteoblast and osteoclast differentiation that are mediated through RXR.

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Tài liệu tham khảo

10.1172/JCI200419900

10.1210/en.2004-0735

10.1021/tx500433r

10.1210/me.2012-1368

10.1002/jbmr.141

10.1007/s11914-006-0002-9

10.1002/jcp.24705

10.1677/JOE-10-0209

10.1016/j.tox.2008.03.025

10.1016/j.marpolbul.2007.12.009

10.1016/j.bcp.2010.12.023

10.1016/j.chemosphere.2004.09.092

10.1359/jbmr.2003.18.9.1584

10.1210/me.2005-0367

10.1152/physrev.00008.2012

10.1124/mol.104.008409

10.1021/es990011w

10.1007/s00244-010-9513-6

10.1074/jbc.M110.123281

10.1189/jlb.1112601

10.1210/me.2009-0261

10.1002/jbmr.1702

10.1016/S0092-8674(00)81569-X

10.1210/en.2006-1587

10.1016/j.bone.2005.07.008

10.1038/embor.2009.8

10.1002/(SICI)1097-4644(19990901)74:3<357::AID-JCB5>3.0.CO;2-7

10.1093/toxsci/kfu197

10.1242/dev.126227

10.1016/S0960-0760(03)00074-8

10.1172/JCI77186

10.1248/jhs.54.224

10.1038/nm.2489

10.1006/enrs.2001.4321

10.1093/nar/29.9.e45

10.1371/journal.pone.0051746

10.1074/jbc.M111.235937

Rios H. F., 2005, DMP1 is essential for osteocyte formation and function, Journal of Musculoskeletal and Neuronal Interactions, 5, 325

10.1359/jbmr.060503

10.1210/en.2003-0746

10.1007/s00223-003-0101-x

10.1016/S0269-7491(99)00068-8

10.1007/s00223-014-9865-4

10.1093/nar/22.25.5628

10.1016/j.bcp.2004.04.020

10.1359/jbmr.080706

10.1038/nm1672

10.1016/j.tox.2015.03.006

10.1016/j.cmet.2010.04.015

10.1101/gad.9.9.1033

10.1096/fj.08-118976

10.1093/toxsci/kfr140

10.1073/pnas.95.7.3597

10.1016/j.bbrc.2006.12.237

10.1371/journal.pone.0086757

10.1038/358587a0

10.1371/journal.pone.0102706

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Journal of Cellular Physiology

Tập 233 Số 9

7007-7021

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