title: Unveiling the bmp13 enigma: redundant morphogen or crucial regulator?
abstract: Bone morphogenetic proteins are a diverse group of morphogens with influences not only on bone tissue, as the nomenclature suggests, but on multiple tissues in the body and often at crucial and influential periods in development. The purpose of this review is to identify and discuss current knowledge of one vertebrate BMP, Bone Morphogenetic Protein 13 (BMP13), from a variety of research fields, in order to clarify BMP13's functional contribution to developing and maintaining healthy tissues, and to identify potential future research directions for this intriguing morphogen. BMP13 is highly evolutionarily conserved (active domain >95%) across diverse species from Zebrafish to humans, suggesting a crucial function. In addition, mutations in BMP13 have recently been associated with Klippel-Feil Syndrome, causative of numerous skeletal and developmental defects including spinal disc fusion. The specific nature of BMP13's crucial function is, however, not yet known.The literature for BMP13 is focused largely on its activity in the healing of tendon-like tissues, or in comparisons with other BMP family molecules for whom a clear function in embryo development or osteogenic differentiation has been identified. There is a paucity of detailed information regarding BMP13 protein activity, structure or protein processing. Whilst some activity in the stimulation of osteogenic or cartilaginous gene expression has been reported, and BMP13 expression is found in post natal cartilage and tendon tissues, there appears to be a redundancy of function in the BMP family, with several members capable of stimulating similar tissue responses. This review aims to summarise the known or potential role(s) for BMP13 in a variety of biological systems.
authors.affiliation: Spine Service, St George Clinical School, University of New South Wales, Sydney, Australia. l.williams@spine-service.org
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Williams
authors.forename: Divya
authors.initials: D
authors.lastname: Bhargav
authors.forename: Ashish D
authors.initials: AD
authors.lastname: Diwan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D020869:Gene Expression Profiling; D055431:Growth Differentiation Factor 6 / Q000145:classification / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D055431:Growth Differentiation Factor 6
references.citation: J Cell Biochem. 2005 May 1;95(1):173-88
references.pmid: 15759275
references.citation: Mech Dev. 1997 Jan;61(1-2):199-212
references.pmid: 9076689
references.citation: Biochem Biophys Res Commun. 2005 Mar 18;328(3):651-7
references.pmid: 15694398
references.citation: Ann N Y Acad Sci. 2006 Apr;1068:41-53
references.pmid: 16831904
references.citation: Osteoarthritis Cartilage. 2002 May;10(5):394-401
references.pmid: 12027540
references.citation: Science. 1988 Dec 16;242(4885):1528-34
references.pmid: 3201241
references.citation: Mol Biol Cell. 2004 Nov;15(11):5012-20
references.pmid: 15356272
references.citation: Matrix Biol. 1995 Oct;14(8):599-606
references.pmid: 9057810
references.citation: Mech Dev. 1995 Feb;49(3):223-34
references.pmid: 7734395
references.citation: J Biol Chem. 2006 Nov 10;281(45):34021-31
references.pmid: 16966322
references.citation: Development. 1999 Nov;126(22):4977-87
references.pmid: 10529416
references.citation: Science. 1996 Nov 22;274(5291):1389-91
references.pmid: 8910282
references.citation: J Anat. 2003 Mar;202(Pt 3):269-77
references.pmid: 12713267
references.citation: Dev Biol. 2002 Oct 15;250(2):231-50
references.pmid: 12376100
references.citation: Bone. 1999 Jul;25(1):91-3
references.pmid: 10423029
references.citation: BMC Dev Biol. 2006 Sep 29;6:43
references.pmid: 17010201
references.citation: J Cell Biol. 1996 Jul;134(1):181-91
references.pmid: 8698813
references.citation: Endocrinology. 2001 May;142(5):2087-94
references.pmid: 11316776
references.citation: Am J Hum Genet. 2007 Feb;80(2):306-15
references.pmid: 17236135
references.citation: Teratology. 1996 Mar;53(3):152-7
references.pmid: 8761882
references.citation: Nat Rev Mol Cell Biol. 2000 Dec;1(3):169-78
references.pmid: 11252892
references.citation: J Neurosurg. 2001 Aug;95(2):298-307
references.pmid: 11780901
references.citation: Arthritis Rheum. 1998 Feb;41(2):263-73
references.pmid: 9485084
references.citation: Cell. 1993 May 7;73(3):421-4
references.pmid: 8490958
references.citation: J Orthop Sci. 2003;8(6):829-35
references.pmid: 14648273
references.citation: Cytokine. 2000 Nov;12(11):1630-8
references.pmid: 11052813
references.citation: Proc Natl Acad Sci U S A. 1981 Dec;78(12):7599-603
references.pmid: 6950401
references.citation: Pediatr Nephrol. 2000 Jul;14(7):598-601
references.pmid: 10912525
references.citation: J Bone Miner Res. 1998 Mar;13(3):383-92
references.pmid: 9525338
references.citation: Spine (Phila Pa 1976). 2007 Nov 1;32(23):2515-20
references.pmid: 17978648
references.citation: Tissue Eng. 2002 Aug;8(4):591-601
references.pmid: 12201999
references.citation: J Biol Chem. 1994 Nov 11;269(45):28227-34
references.pmid: 7961761
references.citation: J Clin Invest. 1997 Jul 15;100(2):321-30
references.pmid: 9218508
references.citation: J Histochem Cytochem. 2004 Sep;52(9):1151-7
references.pmid: 15314082
references.citation: Pediatr Radiol. 1998 Dec;28(12):967-74
references.pmid: 9880643
references.citation: Mech Dev. 2000 Dec;99(1-2):15-27
references.pmid: 11091070
references.citation: Chem Rev. 2002 Dec;102(12):4525-48
references.pmid: 12475200
references.citation: Bone. 1996 Dec;19(6):569-74
references.pmid: 8968021
references.citation: Mech Dev. 1998 Jun;74(1-2):75-88
references.pmid: 9651485
references.citation: Bone. 1998 Jun;22(6):591-603
references.pmid: 9626397
references.citation: Exp Biol Med (Maywood). 2007 Sep;232(8):979-92
references.pmid: 17720944
references.citation: J Biol Chem. 1990 Aug 5;265(22):13198-205
references.pmid: 2376592
references.citation: Dev Biol. 1999 May 1;209(1):11-27
references.pmid: 10208739
references.citation: Spine (Phila Pa 1976). 2005 Dec 1;30(23):2601-7
references.pmid: 16319745
references.citation: Cell Signal. 2004 Mar;16(3):291-9
references.pmid: 14687659
references.citation: Development. 1996 Nov;122(11):3557-66
references.pmid: 8951071
references.citation: Arthritis Res. 2001;3(1):1-5
references.pmid: 11178121
references.citation: J Biol Chem. 2005 Sep 16;280(37):32122-32
references.pmid: 16049014
references.citation: Development. 1999 Aug;126(15):3347-57
references.pmid: 10393114
references.citation: J Cell Physiol. 2004 Dec;201(3):401-8
references.pmid: 15389555
references.citation: Mol Reprod Dev. 1992 Jun;32(2):160-7
references.pmid: 1637554
references.citation: Genes Dev. 1994 Nov 1;8(21):2588-601
references.pmid: 7958918
references.citation: Spine (Phila Pa 1976). 2006 Sep 1;31(19):2173-9
references.pmid: 16946650
references.citation: Med Sci Sports Exerc. 2001 May;33(5):685-7
references.pmid: 11323533
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4363-5
references.pmid: 12682283
references.citation: Kidney Int. 2000 Jun;57(6):2207-14
references.pmid: 10844590
references.citation: Dev Biol. 2003 Feb 1;254(1):116-30
references.pmid: 12606286
references.citation: Nature. 2005 Mar 10;434(7030):229-34
references.pmid: 15759004
references.citation: EMBO J. 1998 Aug 17;17(16):4735-43
references.pmid: 9707432
references.citation: Spine (Phila Pa 1976). 1992 Aug;17(8):874-8
references.pmid: 1523489
references.citation: J Bone Miner Res. 2004 Jan;19(1):111-22
references.pmid: 14753743
references.citation: Endocr Rev. 2003 Apr;24(2):218-35
references.pmid: 12700180
references.citation: Acta Orthop. 2005 Jun;76(3):421-7
references.pmid: 16156473
references.citation: J Orthop Res. 2003 Jul;21(4):617-21
references.pmid: 12798060
references.citation: Mol Cell Biol. 1994 Jun;14(6):3810-21
references.pmid: 8196624
references.citation: Development. 2001 Mar;128(6):965-72
references.pmid: 11222150
references.citation: Dev Biol. 2001 Nov 1;239(1):1-14
references.pmid: 11784015
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3315-20
references.pmid: 12601179
references.citation: Development. 1996 Dec;122(12):3969-79
references.pmid: 9012517
references.citation: Semin Cell Dev Biol. 1999 Jun;10(3):319-26
references.pmid: 10441546
references.citation: Clin Orthop Relat Res. 1998 Jan;(346):26-37
references.pmid: 9577407
references.citation: Nature. 1994 Apr 14;368(6472):639-43
references.pmid: 8145850
references.citation: Spine (Phila Pa 1976). 1990 Aug;15(8):762-7
references.pmid: 2237626
references.citation: Cytokine Growth Factor Rev. 2005 Jun;16(3):309-17
references.pmid: 15951218
references.citation: Hum Mutat. 2008 Aug;29(8):1017-27
references.pmid: 18425797
references.citation: J Biol Chem. 2005 Jul 29;280(30):27970-80
references.pmid: 15929982
references.citation: Biochem Biophys Res Commun. 2007 Oct 26;362(3):550-3
references.pmid: 17719560
references.citation: Biochem Biophys Res Commun. 1995 May 25;210(3):670-7
references.pmid: 7763240
references.citation: Genes Dev. 2001 Nov 1;15(21):2797-802
references.pmid: 11691831
references.citation: Development. 1999 Jan;126(2):241-50
references.pmid: 9847238
references.citation: Biochem Biophys Res Commun. 1995 Apr 26;209(3):859-66
references.pmid: 7733977
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2905-9
references.pmid: 8464906
references.citation: J Orthop Res. 2002 Nov;20(6):1170-4
references.pmid: 12472225
references.citation: Dev Biol. 1999 Jun 15;210(2):251-68
references.pmid: 10357889
references.citation: Ann Rheum Dis. 2006 Feb;65(2):169-77
references.pmid: 15975973
references.citation: Science. 1965 Nov 12;150(3698):893-9
references.pmid: 5319761
references.citation: Biochem Biophys Res Commun. 1997 Mar 6;232(1):153-6
references.pmid: 9125121
references.citation: Arch Otolaryngol Head Neck Surg. 1999 Aug;125(8):901-6
references.pmid: 10448738