Glucocorticoid-dependent Wnt signaling by mature osteoblasts is a key regulator of cranial skeletal development in mice

Development
Hong ZhouMarkus J Seibel

Abstract

Glucocorticoids are important regulators of bone cell differentiation and mesenchymal lineage commitment. Using a cell-specific approach of osteoblast-targeted transgenic disruption of intracellular glucocorticoid signaling, we discovered a novel molecular pathway by which glucocorticoids, mainly through the mature osteoblast, regulate the cellular mechanisms that govern cranial skeleton development. Embryonic and neonatal transgenic mice revealed a distinct phenotype characterized by hypoplasia and osteopenia of the cranial skeleton; disorganized frontal, parietal and interparietal bones; increased suture patency; ectopic differentiation of cartilage in the sagittal suture; and disturbed postnatal removal of parietal cartilage. Concurrently, expression of Mmp14, an enzyme essential for calvarial cartilage removal, was markedly reduced in parietal bone and cartilage of transgenic animals. Expression of Wnt9a and Wnt10b was significantly reduced in osteoblasts with disrupted glucocorticoid signaling, and accumulation of beta-catenin, the upstream regulator of Mmp14 expression, was decreased in osteoblasts, chondrocytes and mesenchymal progenitors of transgenic mice. Supracalvarial injection of Wnt3a protein rescued the transgeni...Continue Reading

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Citations

Jun 19, 2013·Molecular and Cellular Endocrinology·Ulrike BaschantJan Tuckermann
Mar 14, 2014·The Lancet. Diabetes & Endocrinology·Markus J SeibelHong Zhou
Mar 31, 2011·Acta Physiologica·P WendG A Miranda-Carboni
Oct 25, 2012·The Journal of Clinical Investigation·Tara C Brennan-SperanzaMarkus J Seibel
Jan 15, 2014·Trends in Endocrinology and Metabolism : TEM·Holger HenneickeMarkus J Seibel
Feb 5, 2014·BMC Musculoskeletal Disorders·Cornelia M SpiesFrank Buttgereit
Nov 28, 2012·Cellular and Molecular Life Sciences : CMLS·H Sadie-Van GijsenW F Ferris
Nov 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Si Hui TanRoeland Nusse
Jul 30, 2010·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Le LinGuang-Yu Fan
Sep 11, 2009·Clinical Endocrinology·Markus Herrmann, Markus J Seibel
Dec 9, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anna E RappAnita Ignatius
Mar 29, 2018·Journal of Molecular Endocrinology·Yasmine HachemiJan Tuckermann
Mar 10, 2018·Journal of Periodontology·Atika Resti FitriPiyamas Sumrejkanchanakij
Nov 13, 2018·Journal of Cellular Physiology·Lufei WangHu Long
May 30, 2009·Molecular Endocrinology·Lorenz C Hofbauer, Martina Rauner
Jun 1, 2013·Bone Research·Hong ZhouMarkus J Seibel
Jan 25, 2018·Molecular Medicine Reports·Shaokun ZhangQingwei Liang
May 20, 2020·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Ugur M AyturkMatthew L Warman
Feb 5, 2016·Physiological Reviews·Kerstin HartmannJan P Tuckermann
Nov 5, 2019·Frontiers in Immunology·Mubashir AhmadJan Tuckermann
Sep 27, 2018·Frontiers in Endocrinology·Paula Suarez-BreguaJosep Rotllant
Feb 28, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Martina BlaschkeHeide Siggelkow
Sep 24, 2020·Bone Research·Eugenie MacfarlaneHong Zhou
May 19, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·John GarciaAnne M Delany
Jun 5, 2021·Experimental Cell Research·Ryosuke NakamuraRyan C Branski

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