title: From collagen chemistry towards cell therapy - a personal journey.
abstract: The Fell-Muir Award requires the recipient to deliver a lecture and a review manuscript which provides a personal overview of significant scientific developments in the field of matrix biology over the period of the recipient's career. In this context, this review considers the collagen family of structural proteins and the advances in biochemical, molecular biological and genetic techniques which led to the elucidation of the structure, synthesis and function of this important group of extracellular matrix constituents. Particular attention is focussed on early research on the identification and assembly of the soluble precursors of collagen types I and II, and the identification of the precursor of basement membrane collagen type IV. In subsequent studies investigating the maintenance of the chick chondrocyte phenotype in culture, the influence of the extracellular milieu was found to influence markedly both cell morphology and collagen gene expression. These studies led to the discovery of collagen type X whose expression is restricted to hypertrophic chondrocytes at sites of endochondral ossification. Such research provided a prelude to investigations of mammalian endochondral ossification which is known to be aberrant in a variety of human chondrodysplasias and is reactivated in bone fracture repair and in osteoarthritis. The cloning of bovine and then human collagen type X genes facilitated studies in relevant human diseases and contributed to the discovery of mutations in the COL10A1 gene in families with metaphyseal chondrodysplasia type Schmid. Clustering of mutations in the C-terminal domain of the type X collagen molecule has now been widely documented and investigations of the pathogenic mechanisms in animal models are beginning to suggest the prospect of novel treatment strategies.
authors: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Manchester, UK. michael.grant@manchester.ac.uk
authors: Michael E
authors: ME
authors: Grant
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry* / Q000502:physiology; D024121:Collagen Type X / Q000235:genetics; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism* / Q000628:therapy
chemical_list: D024121:Collagen Type X; D003094:Collagen
references: FEBS Lett. 1992 Jun 1;303(2-3):126-8
references: 1607009
references: Biochem J. 1977 Feb 1;161(2):405-18
references: 192195
references: Essays Biochem. 1976;12:77-113
references: 188639
references: J Cell Biol. 1991 Aug;114(3):597-604
references: 1860888
references: Hum Mutat. 2002 May;19(5):465-78
references: 11968079
references: Biochem Soc Trans. 2000;28(4):311-39
references: 10961914
references: Biochem J. 1971 Jan;121(2):197-202
references: 5000644
references: Biochem J. 1991 Jan 1;273(Pt 1):141-8
references: 1703407
references: Int J Biochem Cell Biol. 1997 Oct;29(10):1145-8
references: 9438378
references: FEBS Lett. 1987 Aug 10;220(1):181-6
references: 2440723
references: Expert Rev Mol Med. 2006 Aug 08;8(19):1-23
references: 16893474
references: FEBS Lett. 1975 Sep 1;57(1):47-50
references: 1236811
references: Semin Cell Dev Biol. 1999 Oct;10(5):455-64
references: 10597628
references: Bioessays. 2003 Feb;25(2):142-51
references: 12539240
references: Biochem J. 1991 Dec 15;280 ( Pt 3):617-23
references: 1764025
references: Am J Hum Genet. 1994 Feb;54(2):169-78
references: 8304336
references: J Cell Biol. 1989 Oct;109(4 Pt 1):1849-56
references: 2477383
references: Proc Natl Acad Sci U S A. 1954 Aug;40(8):679-88
references: 16589538
references: J Cell Sci. 1990 Apr;95 ( Pt 4):639-48
references: 2200798
references: Science. 1996 Nov 22;274(5291):1292-5
references: 8966595
references: Biochem Biophys Res Commun. 1973 May 1;52(1):115-20
references: 4712181
references: Science. 2006 Aug 25;313(5790):1137-40
references: 16931765
references: J Cell Biol. 1990 Jan;110(1):219-27
references: 2104858
references: Biochem J. 1968 Jul;108(4):587-91
references: 5667271
references: Biochem J. 1979 Jul 15;182(1):81-93
references: 227370
references: In Vitro Cell Dev Biol. 1987 May;23(5):374-80
references: 3583986
references: Biochem J. 1985 Apr 15;227(2):545-54
references: 4004779
references: FASEB J. 1989 Mar;3(5):1609-17
references: 2537773
references: Biochem J. 1983 May 1;211(2):417-26
references: 6870839
references: J Cell Sci. 1991 Jul;99 ( Pt 3):641-9
references: 1939374
references: Biogr Mem Fellows R Soc. 1987;33:237-59
references: 11621435
references: Am J Hum Genet. 1992 Oct;51(4):841-9
references: 1329505
references: Annu Rev Biophys Biophys Chem. 1991;20:137-52
references: 1867713
references: PLoS Biol. 2007 Mar;5(3):e44
references: 17298185
references: Biosci Rep. 1988 Apr;8(2):163-71
references: 3408812
references: Proc Natl Acad Sci U S A. 1972 Jan;69(1):60-4
references: 4333046
references: Nature. 1955 Jan 8;175(4445):70-4
references: 13223793
references: J Biol Chem. 1973 Nov 10;248(21):7432-7
references: 4583355
references: Prog Retin Eye Res. 2000 May;19(3):323-44
references: 10749380
references: N Engl J Med. 1984 Aug 9;311(6):376-86
references: 6146097
references: Bone Miner. 1991 Nov;15(2):151-63
references: 1764631
references: N Engl J Med. 1979 Jul 12;301(2):77-85
references: 36559
references: Biochem J. 1996 May 15;316 ( Pt 1):1-11
references: 8645190
references: FEBS Lett. 1984 Apr 24;169(2):179-84
references: 6425083
references: N Engl J Med. 1972 Jan 27;286(4):194-9
references: 4257078
references: J Cell Biol. 1975 Dec;67(3):835-51
references: 811671
references: Hum Mol Genet. 2003 Feb 1;12(3):217-25
references: 12554676
references: Int Rev Connect Tissue Res. 1970;5:93-163
references: 5533228
references: Am J Hum Genet. 2003 Sep;73(3):447-74
references: 12900795
references: N Engl J Med. 1992 Feb 20;326(8):540-6
references: 1732793
references: J Biol Chem. 1972 Jun 10;247(11):3545-51
references: 4555424
references: Z Kardiol. 2000;89 Suppl 2:20-7
references: 10769400
references: J Cell Biol. 1982 Jun;93(3):767-74
references: 6811598
references: Int Rev Connect Tissue Res. 1981;9:191-264
references: 7040276
references: Hum Mutat. 2005 Jun;25(6):525-34
references: 15880705
references: EMBO J. 1997 Mar 3;16(5):908-16
references: 9118952
references: J Biol Chem. 1972 Jun 10;247(11):3539-44
references: 4337858
references: Int Rev Connect Tissue Res. 1963;1:63-125
references: 14110870