title: Hypoxia, HIFs and bone development.
abstract: Oxygen is not only an obviously important substrate, but it is also a regulatory signal that controls expression of a specific genetic program. Crucial mediator of the adaptive response of cells to hypoxia is the family of Hypoxia-Inducible Transcription Factors (HIFs).The fetal growth plate, which is an avascular structure of mesenchymal origin, has a unique out-in gradient of oxygenation. HIF-1alpha is necessary for chondrogenesis in vivo by controlling a complex homeostatic response that allows chondrocytes to survive and differentiate in a hypoxic environment. Moreover, HIFs are also essential in osteogenesis and joint development. This brief Perspective summarizes the critical role of HIFs in endochondral bone development.
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Araldi
authors.forename: Ernestina
authors.initials: E
authors.lastname: Schipani
mesh_terms: D000818:Animals; D001846:Bone Development / Q000502:physiology*; D015687:Cell Hypoxia; D020219:Chondrogenesis / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D007596:Joints / Q000378:metabolism; D008954:Models, Biological
chemical_list: D051793:Hypoxia-Inducible Factor 1
references.citation: Osteoarthritis Cartilage. 2004 Apr;12(4):336-45
references.pmid: 15023385
references.citation: Dev Cell. 2005 Nov;9(5):617-28
references.pmid: 16256737
references.citation: J Neurosci. 2000 Oct 1;20(19):7377-83
references.pmid: 11007896
references.citation: Arthritis Rheum. 2009 May;60(5):1406-15
references.pmid: 19404942
references.citation: Prog Biophys Mol Biol. 2006 Jul;91(3):249-86
references.pmid: 16137743
references.citation: Development. 2004 May;131(10):2497-508
references.pmid: 15128677
references.citation: Dev Cell. 2001 Aug;1(2):277-90
references.pmid: 11702786
references.citation: FEBS Lett. 2009 Mar 18;583(6):1006-10
references.pmid: 19233176
references.citation: Clin Cancer Res. 2008 Mar 1;14(5):1340-8
references.pmid: 18316553
references.citation: Cell. 1997 May 30;89(5):747-54
references.pmid: 9182762
references.citation: Mol Cell Biol. 2005 Jun;25(11):4565-78
references.pmid: 15899860
references.citation: Cancer Res. 2005 Apr 15;65(8):3299-306
references.pmid: 15833863
references.citation: Genes Dev. 2004 Sep 15;18(18):2183-94
references.pmid: 15371333
references.citation: Proc Natl Acad Sci U S A. 2002 May 14;99(10):7021-6
references.pmid: 12011461
references.citation: Mol Cell Biol. 2000 Jun;20(11):4149-58
references.pmid: 10805756
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1949-54
references.pmid: 18238902
references.citation: J Cell Biol. 2007 May 7;177(3):451-64
references.pmid: 17470636
references.citation: Genes Dev. 2001 Oct 15;15(20):2675-86
references.pmid: 11641274
references.citation: Dev Cell. 2002 Mar;2(3):331-41
references.pmid: 11879638
references.citation: EMBO J. 2010 Jan 20;29(2):424-41
references.pmid: 20010698
references.citation: Mol Cell Biol. 2005 Apr;25(8):3040-55
references.pmid: 15798192
references.citation: Mol Cell. 2009 Sep 24;35(6):737-8
references.pmid: 19782023
references.citation: Nat Genet. 2003 Dec;35(4):331-40
references.pmid: 14608355
references.citation: Autophagy. 2008 Feb;4(2):195-204
references.pmid: 18059169
references.citation: J Biol Chem. 2008 Apr 18;283(16):10892-903
references.pmid: 18281291
references.citation: Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):539-46
references.pmid: 16144691
references.citation: J Biol Chem. 2009 Apr 24;284(17):11326-35
references.pmid: 19251704
references.citation: J Biol Chem. 2003 Aug 15;278(33):30772-80
references.pmid: 12788921
references.citation: Genes Dev. 2002 Nov 1;16(21):2813-28
references.pmid: 12414734
references.citation: Development. 2004 May;131(9):2161-71
references.pmid: 15073147
references.citation: J Cell Mol Med. 2008 Sep-Oct;12(5A):1426-31
references.pmid: 18624759
references.citation: Cancer Cell. 2009 Jan 6;15(1):35-44
references.pmid: 19111879
references.citation: Nat Rev Mol Cell Biol. 2008 Apr;9(4):285-96
references.pmid: 18285802
references.citation: J Biol Chem. 2002 Sep 6;277(36):32405-8
references.pmid: 12119283
references.citation: Cell Cycle. 2009 Sep 1;8(17):2756-68
references.pmid: 19652553
references.citation: Birth Defects Res C Embryo Today. 2005 Sep;75(3):200-12
references.pmid: 16187326
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61
references.pmid: 16461460
references.citation: J Cell Biochem. 2010 Jan 1;109(1):196-204
references.pmid: 19899108
references.citation: Nature. 2003 May 15;423(6937):332-6
references.pmid: 12748651
references.citation: Plast Reconstr Surg. 1999 Sep;104(3):738-47
references.pmid: 10456527
references.citation: Autophagy. 2007 May-Jun;3(3):207-14
references.pmid: 17224629
references.citation: FASEB J. 2003 Feb;17(2):271-3
references.pmid: 12490539
references.citation: Dev Biol. 2009 Aug 15;332(2):196-211
references.pmid: 19464280
references.citation: Mol Cell Biol. 2007 Mar;27(5):1859-67
references.pmid: 17194750
references.citation: J Clin Invest. 2007 Jun;117(6):1616-26
references.pmid: 17549257
references.citation: Bone. 2005 Sep;37(3):313-22
references.pmid: 16023419
references.citation: J Biol Chem. 2004 Oct 1;279(40):41966-74
references.pmid: 15280364
references.citation: Science. 2001 Apr 20;292(5516):464-8
references.pmid: 11292862
references.citation: Development. 2002 Apr;129(8):1893-904
references.pmid: 11934855
references.citation: Mol Cell Biol. 2003 Jan;23(1):359-69
references.pmid: 12482987
references.citation: Cell Death Differ. 2008 Apr;15(4):619-20
references.pmid: 18345017
references.citation: Biochem Biophys Res Commun. 2008 Oct 24;375(3):287-91
references.pmid: 18680722
references.citation: Cancer Res. 2008 Jul 15;68(14):5540-5
references.pmid: 18632605
references.citation: Genes Dev. 2001 Nov 1;15(21):2865-76
references.pmid: 11691837
references.citation: J Cell Biol. 2005 May 23;169(4):681-91
references.pmid: 15911882
references.citation: J Biol Chem. 2006 Oct 13;281(41):30678-83
references.pmid: 16926163
references.citation: EMBO J. 2004 May 5;23(9):1949-56
references.pmid: 15071503
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):686-91
references.pmid: 18184809
references.citation: Biochem Biophys Res Commun. 2005 Mar 18;328(3):658-65
references.pmid: 15694399
references.citation: Genes Dev. 2002 Jun 15;16(12):1466-71
references.pmid: 12080085
references.citation: Nature. 2003 May 15;423(6937):316-8
references.pmid: 12748648
references.citation: J Orthop Res. 2000 Sep;18(5):698-705
references.pmid: 11117289
references.citation: J Biol Chem. 2009 Oct 23;284(43):29514-25
references.pmid: 19706597
references.citation: Mol Cell Biol. 2007 Sep;27(17):6229-42
references.pmid: 17576813
references.citation: Clin Orthop Relat Res. 1990 Jan;(250):8-26
references.pmid: 2403497
references.citation: Ann N Y Acad Sci. 2007 Nov;1117:26-39
references.pmid: 18056035
references.citation: Cell. 1998 May 1;93(3):411-22
references.pmid: 9590175
references.citation: Ann N Y Acad Sci. 2003 May;995:183-90
references.pmid: 12814950
references.citation: J Neurosci. 2000 Oct 1;20(19):7370-6
references.pmid: 11007895
references.citation: J Biol Chem. 2008 Feb 22;283(8):4778-86
references.pmid: 18077449
references.citation: Mol Cell Biol. 2005 Dec;25(23):10479-91
references.pmid: 16287860
references.citation: Cell. 2007 Oct 19;131(2):324-36
references.pmid: 17956733
references.citation: Trends Mol Med. 2006 Apr;12(4):141-3
references.pmid: 16513423
references.citation: Science. 2001 Nov 9;294(5545):1337-40
references.pmid: 11598268
references.citation: Mol Cell Biol. 2010 Jan;30(1):344-53
references.pmid: 19858293
references.citation: Mol Cell Biol. 2003 Dec;23(24):9361-74
references.pmid: 14645546
references.citation: J Bone Miner Res. 2008 May;23(5):596-609
references.pmid: 18433297
references.citation: Br J Haematol. 2008 May;141(3):325-34
references.pmid: 18410568
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Cell Cycle. 2004 Jul;3(7):853-4
references.pmid: 15190211
references.citation: Nature. 2006 Apr 27;440(7088):1222-6
references.pmid: 16642001
references.citation: Cardiovasc Res. 2003 Dec 1;60(3):569-79
references.pmid: 14659802
references.citation: Cell. 2003 Dec 26;115(7):787-98
references.pmid: 14697198
references.citation: Cell Cycle. 2006 Mar;5(5):495-8
references.pmid: 16552177
references.citation: J Biol Chem. 2007 May 4;282(18):13672-9
references.pmid: 17360716
references.citation: J Cell Physiol. 2007 Feb;210(2):279-89
references.pmid: 17096367
references.citation: PLoS One. 2006 Dec 27;1:e116
references.pmid: 17205120
references.citation: Autophagy. 2006 Jul-Sep;2(3):215-6
references.pmid: 16874108
references.citation: Science. 2001 Apr 20;292(5516):468-72
references.pmid: 11292861
references.citation: Nat Rev Cancer. 2008 Nov;8(11):851-64
references.pmid: 18846101
references.citation: Gene Regul Syst Bio. 2008 Apr 22;2:177-91
references.pmid: 19787082
references.citation: Mol Cell Biol. 2005 Jul;25(13):5675-86
references.pmid: 15964822
references.citation: Mol Cell Biol. 1992 Dec;12(12):5447-54
references.pmid: 1448077
references.citation: Dev Cell. 2009 Dec;17(6):755-73
references.pmid: 20059947
references.citation: Science. 2002 Feb 1;295(5556):858-61
references.pmid: 11823643
references.citation: Cell Death Differ. 2008 Apr;15(4):672-7
references.pmid: 18188166
references.citation: Development. 2009 Apr;136(8):1263-72
references.pmid: 19261698
references.citation: Pediatr Endocrinol Rev. 2003 Sep;1(1):2-8
references.pmid: 16437008
references.citation: Development. 2007 Nov;134(21):3917-28
references.pmid: 17913788
references.citation: Biochem J. 2008 Dec 15;416(3):387-94
references.pmid: 18713068
references.citation: Arthritis Rheum. 2007 Oct;56(10):3297-306
references.pmid: 17907154
references.citation: J Biol Chem. 2004 Sep 17;279(38):40007-16
references.pmid: 15263007
references.citation: Bone. 2009 Jan;44(1):24-31
references.pmid: 18835464
references.citation: Development. 2008 Nov;135(21):3587-97
references.pmid: 18832389
references.citation: Pflugers Arch. 2008 Jan;455(4):563-73
references.pmid: 17849146
references.citation: Nat Med. 1999 Jun;5(6):623-8
references.pmid: 10371499
references.citation: Circ Res. 2009 Apr 10;104(7):879-86
references.pmid: 19265035
references.citation: Cell Death Differ. 2008 Oct;15(10):1572-81
references.pmid: 18551130
references.citation: Ann N Y Acad Sci. 2007 Nov;1116:149-64
references.pmid: 18083926
references.citation: EMBO J. 1998 Sep 1;17(17):5085-94
references.pmid: 9724644
references.citation: Biochem Biophys Res Commun. 2008 Aug 8;372(4):892-7
references.pmid: 18538129