title: Posttranslational modifications of collagens as targets of hypoxia and Hif-1alpha in endochondral bone development.
abstract: In recent years, it has been proposed that oxygen is not only an indispensable metabolic substrate, but also a regulatory signal, and that gradients of oxygenation turn on a specific genetic program. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor hypoxia-inducible factor 1alpha (Hif-1alpha). The fetal growth plate, which is an avascular structure of mesenchymal origin, has a unique out-in gradient of oxygenation. Hif-1alpha is required for chondrogenesis in vivo by controlling a complex homeostatic response that allows chondrocytes to survive and differentiate in an hypoxic environment. Preliminary evidence suggests that regulation of posttranslational modifications of collagens could be an important component of this adaptive response.
authors.affiliation: MGH-Harvard Medical School, Boston, Massachusetts, USA. schipani@helix.mgh.harvard.edu
authors.forename: Ernestina
authors.initials: E
authors.lastname: Schipani
mesh_terms: D000818:Animals; D001846:Bone Development / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D003094:Collagen / Q000378:metabolism*; D006132:Growth Plate / Q000196:embryology / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D003094:Collagen
references.citation: Genes Dev. 2004 Sep 15;18(18):2183-94
references.pmid: 15371333
references.citation: J Cell Biol. 2007 May 7;177(3):451-64
references.pmid: 17470636
references.citation: Obstet Gynecol. 1992 Aug;80(2):283-5
references.pmid: 1635745
references.citation: J Biol Chem. 2003 Aug 15;278(33):30772-80
references.pmid: 12788921
references.citation: Birth Defects Res C Embryo Today. 2005 Sep;75(3):200-12
references.pmid: 16187326
references.citation: Genes Dev. 1998 Jan 15;12(2):149-62
references.pmid: 9436976
references.citation: Nature. 2003 May 15;423(6937):316-8
references.pmid: 12748648
references.citation: J Neurosci. 2000 Oct 1;20(19):7370-6
references.pmid: 11007895
references.citation: Cancer Biol Ther. 2004 Jun;3(6):492-7
references.pmid: 15254394
references.citation: Cell Cycle. 2008 May 1;7(9):1128-32
references.pmid: 18418042
references.citation: Semin Radiat Oncol. 2004 Jul;14(3):207-14
references.pmid: 15254863
references.citation: J Neurosci. 2000 Oct 1;20(19):7377-83
references.pmid: 11007896
references.citation: Development. 2007 Nov;134(21):3917-28
references.pmid: 17913788
references.citation: J Biol Chem. 2004 Sep 17;279(38):40007-16
references.pmid: 15263007
references.citation: Nature. 2006 May 25;441(7092):437-43
references.pmid: 16724055
references.citation: Nat Rev Cancer. 2003 Oct;3(10):721-32
references.pmid: 13130303
references.citation: Ann N Y Acad Sci. 1996 Jun 8;785:124-30
references.pmid: 8702118
references.citation: Genes Dev. 2002 Jun 15;16(12):1441-5
references.pmid: 12080083
references.citation: Dev Cell. 2002 Mar;2(3):331-41
references.pmid: 11879638
references.citation: Mol Cell Biol. 2005 Apr;25(8):3040-55
references.pmid: 15798192
references.citation: Am J Pathol. 2006 Aug;169(2):491-502
references.pmid: 16877351
references.citation: EMBO J. 1998 Jun 1;17(11):3005-15
references.pmid: 9606183
references.citation: Nat Rev Drug Discov. 2003 Oct;2(10):803-11
references.pmid: 14526383
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: Bone. 2005 Sep;37(3):313-22
references.pmid: 16023419
references.citation: PLoS Biol. 2007 Mar;5(3):e44
references.pmid: 17298185
references.citation: Genes Dev. 2001 Nov 1;15(21):2865-76
references.pmid: 11691837
references.citation: J Biol Chem. 2006 Oct 13;281(41):30678-83
references.pmid: 16926163
references.citation: PLoS Biol. 2004 Oct;2(10):e289
references.pmid: 15361934
references.citation: Dev Cell. 2005 Nov;9(5):617-28
references.pmid: 16256737
references.citation: J Pathol. 2005 Jul;206(3):291-304
references.pmid: 15906272
references.citation: Trends Mol Med. 2006 Apr;12(4):141-3
references.pmid: 16513423
references.citation: Mol Cell Biol. 2005 Dec;25(23):10479-91
references.pmid: 16287860
references.citation: Cardiovasc Res. 2003 Dec 1;60(3):569-79
references.pmid: 14659802
references.citation: J Biol Chem. 2007 May 4;282(18):13672-9
references.pmid: 17360716
references.citation: Teratology. 1999 Oct;60(4):215-25
references.pmid: 10508975
references.citation: Glycobiology. 2002 Apr;12(4):57R-68R
references.pmid: 12042245
references.citation: Genes Dev. 2008 Oct 15;22(20):2750-4
references.pmid: 18923073
references.citation: Pediatr Endocrinol Rev. 2003 Sep;1(1):2-8
references.pmid: 16437008