title: Protein kinase D1 is essential for bone acquisition during pubertal growth.
abstract: Bone formation and maintenance represents the summation of the balance of local and endocrine hormonal stimuli within a complex organ. Protein kinase D (PKD) is a member of the Ca(2+)/calmodulin-dependent kinase superfamily of serine/threonine kinases and has been described as the crossroads for the bone morphogenetic protein (BMP)-IGF-I signaling axis, which plays a major role in bone formation. The current study exploits the PKD1-deficient mouse model to examine the role of PKD in vivo in the skeleton. Dual-energy x-ray absorptiometry scan analysis of male and female pubescent mice demonstrated significantly decreased bone mineral density in the whole body and femoral bone compartments of PKD1 (+/-) mice, compared with their wild-type littermates. The body weight, nasal-anal length, and percentage body fat of the mice were not significantly different from their wild-type littermates. Cultured bone marrow stromal cells from PKD1 (+/-) mice demonstrated lower alkaline phosphatase activity in early differentiating osteoblasts and decreased mineralized nodule formation in mature osteoblasts. Quantitative RT-PCR analysis of osteoblast differentiation markers and osteoclast markers exhibited lower levels of expression in PKD1 (+/-) male mice than wild type. In female mice, however, only markers of osteoblast differentiation were reduced. PKD1 (+/-) mice also demonstrated a profound reduction in mRNA expression levels of BMP type II receptor and IGF-I receptor and in BMP-7 responsiveness in vitro. Together these data suggest that in mice, PKD1 action contributes to the regulation of osteoblastogenesis by altering gene expression with gender-specific effects on osteoclastogenesis, subsequently affecting skeletal matrix acquisition during puberty.
authors: PhD, Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229. leej@uthscsa.edu.
authors: Jeffery J
authors: JJ
authors: Ford
authors: Lee-Chuan C
authors: LC
authors: Yeh
authors: Eric C
authors: EC
authors: Schmidgal
authors: Jason F
authors: JF
authors: Thompson
authors: Martin L
authors: ML
authors: Adamo
authors: John C
authors: JC
authors: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D015519:Bone Density; D001846:Bone Development / Q000502:physiology*; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D012741:Sexual Maturation / Q000502:physiology; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; C089212:protein kinase D; D011493:Protein Kinase C; D000469:Alkaline Phosphatase
references: Biochim Biophys Acta. 1999 May 6;1450(1):99-106
references: 10231560
references: Steroids. 2013 May;78(5):513-20
references: 23499826
references: Pediatr Nephrol. 2000 Jul;14(7):598-601
references: 10912525
references: Curr Osteoporos Rep. 2012 Jun;10(2):178-86
references: 22544603
references: J Cell Biochem. 2012 Mar;113(3):967-76
references: 22034075
references: Endocrinology. 1996 May;137(5):1921-31
references: 8612532
references: Growth Factors. 2009 Apr;27(2):121-31
references: 19180354
references: J Biol Chem. 2013 Apr 5;288(14):9826-9834
references: 23430742
references: Biochem J. 2010 Nov 15;432(1):153-63
references: 20819079
references: Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1376-82
references: 19520973
references: Trends Pharmacol Sci. 2006 Jun;27(6):317-23
references: 16678913
references: Clin Orthop Relat Res. 1998 Jan;(346):26-37
references: 9577407
references: Physiology (Bethesda). 2011 Feb;26(1):23-33
references: 21357900
references: J Biol Chem. 2009 Jan 23;284(4):2225-34
references: 19029091
references: J Biol Chem. 2001 Feb 2;276(5):3310-8
references: 11062248
references: J Biol Chem. 2002 Nov 15;277(46):44005-12
references: 12215457
references: Growth Factors. 2010 Oct;28(5):318-28
references: 20380591
references: J Bone Miner Res. 2010 Dec;25(12):2543-52
references: 20836088
references: Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8572-6
references: 8078925
references: J Bone Miner Res. 2012 Sep;27(9):2001-14
references: 22589223
references: FEBS Lett. 2007 Apr 3;581(7):1377-82
references: 17349631
references: Chem Rev. 2001 Aug;101(8):2353-64
references: 11749377
references: Int J Oncol. 2012 Jun;40(6):1839-48
references: 22426824
references: J Biol Chem. 2004 Jan 2;279(1):259-64
references: 14573624
references: Mol Cell Biol. 2006 Feb;26(4):1569-77
references: 16449666
references: Gene. 2005 Jan 31;345(2):225-35
references: 15716114
references: Sci Signal. 2010 Feb 02;3(107):mr1
references: 20124549
references: J Biol Chem. 2005 Sep 9;280(36):31353-9
references: 16000303
references: Ann N Y Acad Sci. 2010 Mar;1192:286-91
references: 20392248