title: Dexamethasone induces osteogenesis via regulation of hedgehog signalling molecules in rat mesenchymal stem cells.
abstract: OBJECTIVE
  Hedgehog signalling plays an important role during the development of tissues and organs, including bone and limb. Dexamethasone (DEX), a synthetic and widely used glucocorticoid, affects osteogenesis of bone marrow mesenchymal stem cells (MSCs), while the signalling pathway by which DEX affects osteoblast differentiation remains obscure. This study aimed to investigate expressions of hedgehog signalling molecules Shh, Ihh and Gli1 during DEX-induced osteogenesis of rat MSCs in vitro.
  
  
  METHODS
  DEX promoted osteoblast differentiation of MSCs at 10(-8) mol/L from seven days to 21 days, demonstrated by enhancing alkaline phosphatase (ALP) activity and osteoblast-associated marker type I collagen expression during osteoblastic differentiation. Gene and protein expressions of hedgehog signalling molecules, Shh, Ihh and Gli1 were tested by RT-PCR and western blot analysis during osteoblast differentiation.
  
  
  RESULTS
  Shh expression was increased compared to the control while Ihh and Gli1 expressions were decreased on both mRNA and protein level during DEX-induced osteoblast differentiation of MSCs from seven days to 21 days. Altogether, these data demonstrate that DEX can enhance Shh expression via a Gli1-independent mechanism during osteoblast differentiation of MSCs.
  
  
  CONCLUSIONS
  These results indicate that different patterns of hedgehog signalling are involved in DEX-induced osteogenesis and these findings provide insights into the mechanistic link between glucocorticoid-induced osteogenesis and hedgehog signalling pathway.
authors: Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, China.
authors: Xiaoli
authors: X
authors: Ma
authors: Xueping
authors: X
authors: Zhang
authors: Yanfei
authors: Y
authors: Jia
authors: Shanshan
authors: S
authors: Zu
authors: Shuyi
authors: S
authors: Han
authors: Dongjie
authors: D
authors: Xiao
authors: Haiji
authors: H
authors: Sun
authors: Yunshan
authors: Y
authors: Wang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000071676:Zinc Finger Protein GLI1
chemical_list: C498521:Gli1 protein, rat; D005938:Glucocorticoids; D053823:Hedgehog Proteins; C550919:Ihh protein, rat; D051741:Kruppel-Like Transcription Factors; C546888:Shh protein, rat; D000071676:Zinc Finger Protein GLI1; D003907:Dexamethasone; D000469:Alkaline Phosphatase
references: J Bone Miner Res. 2004 Mar;19(3):479-90
references: 15040837
references: Dev Dyn. 2010 Jun;239(6):1818-26
references: 20503377
references: Curr Opin Rheumatol. 2007 Jul;19(4):370-5
references: 17551369
references: Tissue Eng Part C Methods. 2011 Mar;17(3):249-59
references: 20822481
references: J Orthop Sci. 2006 Oct;11(5):491-6
references: 17013738
references: Plast Reconstr Surg. 2011 Mar;127(3):1182-1190
references: 21364421
references: Bone. 2004 Jul;35(1):83-95
references: 15207744
references: Cancer Res. 2006 Aug 1;66(15):7548-53
references: 16885353
references: Curr Osteoporos Rep. 2005 Sep;3(3):98-102
references: 16131429
references: J Clin Invest. 2004 Aug;114(4):485-94
references: 15314685
references: Lab Invest. 2007 May;87(5):499-514
references: 17334411
references: Curr Stem Cell Res Ther. 2009 Dec;4(4):318-29
references: 19804369
references: Ann N Y Acad Sci. 2012 Aug;1266:94-106
references: 22901261
references: Biochem Biophys Res Commun. 2008 Sep 5;373(4):488-92
references: 18572015
references: Crit Rev Eukaryot Gene Expr. 2009;19(1):1-46
references: 19191755
references: Tissue Eng Part A. 2010 Aug;16(8):2605-16
references: 20367246
references: J Steroid Biochem Mol Biol. 2009 Aug;116(1-2):86-92
references: 19460432
references: Dev Cell. 2008 May;14(5):674-88
references: 18477451
references: J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):164-70
references: 18644452
references: Int Orthop. 2011 Apr;35(4):599-605
references: 20414656
references: Handb Exp Pharmacol. 2006;(174):249-82
references: 16370331
references: J Bone Miner Res. 2009 Jan;24(1):50-61
references: 18715135
references: Mol Cell Endocrinol. 2006 Mar 27;248(1-2):87-93
references: 16406260
references: Genesis. 2011 Oct;49(10):784-96
references: 21557453
references: Development. 2009 Dec;136(23):3991-4000
references: 19906866