title: Lrp5 functions in bone to regulate bone mass.
abstract: The human skeleton is affected by mutations in low-density lipoprotein receptor-related protein 5 (LRP5). To understand how LRP5 influences bone properties, we generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high and low bone mass phenotypes in humans. We found that bone properties in these mice were comparable to bone properties in mice with inherited mutations. We also induced an Lrp5 mutation in cells that form the appendicular skeleton but not in cells that form the axial skeleton; we observed that bone properties were altered in the limb but not in the spine. These data indicate that Lrp5 signaling functions locally, and they suggest that increasing LRP5 signaling in mature bone cells may be a strategy for treating human disorders associated with low bone mass, such as osteoporosis.
authors: Orthopedic Research Laboratories, Department of Orthopedic Surgery, Children's Hospital, Boston, Massachusetts, USA.
authors: Yajun
authors: Y
authors: Cui
authors: Paul J
authors: PJ
authors: Niziolek
authors: Bryan T
authors: BT
authors: MacDonald
authors: Cassandra R
authors: CR
authors: Zylstra
authors: Natalia
authors: N
authors: Alenina
authors: Daniel R
authors: DR
authors: Robinson
authors: Zhendong
authors: Z
authors: Zhong
authors: Susann
authors: S
authors: Matthes
authors: Christina M
authors: CM
authors: Jacobsen
authors: Ronald A
authors: RA
authors: Conlon
authors: Robert
authors: R
authors: Brommage
authors: Qingyun
authors: Q
authors: Liu
authors: Faika
authors: F
authors: Mseeh
authors: David R
authors: DR
authors: Powell
authors: Qi M
authors: QM
authors: Yang
authors: Brian
authors: B
authors: Zambrowicz
authors: Han
authors: H
authors: Gerrits
authors: Jan A
authors: JA
authors: Gossen
authors: Xi
authors: X
authors: He
authors: Michael
authors: M
authors: Bader
authors: Bart O
authors: BO
authors: Williams
authors: Matthew L
authors: ML
authors: Warman
authors: Alexander G
authors: AG
authors: Robling
references: Nat Med. 2010 Mar;16(3):308-12
references: 20139991
references: Nat Rev Neurosci. 2006 Oct;7(10):772-83
references: 16988653
references: Hum Mol Genet. 2001 Mar 1;10(5):537-43
references: 11181578
references: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10332-7
references: 19520831
references: Dev Dyn. 2002 Jun;224(2):245-51
references: 12112477
references: J Biol Chem. 2008 Feb 29;283(9):5866-75
references: 18089564
references: Cell. 2008 Nov 28;135(5):795-6
references: 19041744
references: Mol Cell Biol. 2005 Jun;25(12):4946-55
references: 15923613
references: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3299-304
references: 12626757
references: Development. 2004 Nov;131(21):5469-80
references: 15469977
references: Am J Hum Genet. 2001 Mar;68(3):577-89
references: 11179006
references: J Bone Miner Res. 2008 Jun;23(6):860-9
references: 18269310
references: Bone. 2007 Sep;41(3):331-9
references: 17613296
references: Am J Hum Genet. 2003 Mar;72(3):763-71
references: 12579474
references: Biochem Biophys Res Commun. 1998 Oct 29;251(3):784-90
references: 9790987
references: Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17406-11
references: 16293698
references: Bone. 2008 Apr;42(4):606-15
references: 18280232
references: Calcif Tissue Int. 2008 Jun;82(6):445-53
references: 18521528
references: Dev Cell. 2005 May;8(5):739-50
references: 15866164
references: J Biol Chem. 2006 Aug 18;281(33):23698-711
references: 16790443
references: Nucleic Acids Res. 1995 Dec 25;23(24):5080-1
references: 8559668
references: Mol Cell Biol. 2004 Jun;24(11):4677-84
references: 15143163
references: J Bone Miner Res. 2006 Nov;21(11):1738-49
references: 17002572
references: J Bone Miner Res. 2006 Jun;21(6):934-45
references: 16753024
references: Am J Hum Genet. 2005 Nov;77(5):741-53
references: 16252235
references: Genesis. 2002 Jun;33(2):77-80
references: 12112875
references: Neurosci Lett. 2008 Jan 24;431(1):21-5
references: 18082956
references: PLoS One. 2008;3(10):e3301
references: 18923670
references: Genesis. 2007 Sep;45(9):593-605
references: 17868096
references: Cell. 2006 Oct 20;127(2):291-304
references: 17055431
references: Life Sci. 1987 Oct 12;41(15):1777-85
references: 3657383
references: Cell. 2008 Nov 28;135(5):825-37
references: 19041748
references: Genesis. 2000 Nov-Dec;28(3-4):106-10
references: 11105051
references: Am J Hum Genet. 2002 Jan;70(1):11-9
references: 11741193
references: J Bone Miner Res. 2007 Mar;22(3):394-402
references: 17147489
references: Cell. 2001 Nov 16;107(4):513-23
references: 11719191
references: J Bone Miner Res. 2003 Jun;18(6):960-74
references: 12817748
references: J Biol Chem. 2002 Sep 6;277(36):33275-83
references: 12065599
references: Science. 2003 Jan 3;299(5603):76
references: 12511643
references: J Cell Biol. 2002 Apr 15;157(2):303-14
references: 11956231
references: J Dent Res. 2007 Apr;86(4):320-5
references: 17384025
references: Curr Opin Neurobiol. 2008 Feb;18(1):4-11
references: 18513950
references: J Bone Miner Res. 2004 Dec;19(12):2033-40
references: 15537447
references: N Engl J Med. 2002 May 16;346(20):1513-21
references: 12015390
references: Clin Chem. 1985 May;31(5):695-8
references: 3986997
references: N Engl J Med. 2009 Mar 5;360(10):957-9
references: 19264685
references: J Biol Chem. 2006 Oct 20;281(42):31720-8
references: 16908522
references: Dev Cell. 2005 May;8(5):727-38
references: 15866163
references: Development. 2004 Jun;131(12):2803-15
references: 15142971
references: J Pharmacol Exp Ther. 2008 Apr;325(1):47-55
references: 18192499
references: Development. 2005 Jan;132(1):49-60
references: 15576404
references: J Biol Chem. 2006 Dec 15;281(50):38276-84
references: 17052975
references: Mol Cell Biol. 2002 Feb;22(4):1172-83
references: 11809808
references: J Biol Chem. 2007 May 11;282(19):14515-24
references: 17351296
references: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5860-5
references: 8650183
references: J Bone Miner Res. 2006 Nov;21(11):1713-21
references: 17002585