The mammalian chitinase-like lectin, YKL-40, binds specifically to type I collagen and modulates the rate of type I collagen fibril formation.
YKL-40 is expressed in arthritic cartilage and produced in large amounts by cultured chondrocytes, but its exact role is unclear, and the identities of its physiological ligands remain unknown. Purification of YKL-40 from resorbing bovine nasal cartilage and chondrocyte monolayers demonstrated the existence of three isoforms, a major and minor form from resorbing cartilage and a third species from chondrocytes. Affinity chromatography experiments with purified YKL-40 demonstrated specific binding of all three forms to collagen types I, II, and III, thus identifying collagens as potential YKL-40 ligands. Binding to immobilized type I collagen was inhibited by soluble native ligand, but not heat-denatured ligand, confirming a specific interaction. Binding of the chondrocyte-derived species to type I collagen was also demonstrated by surface plasmon resonance analysis, and the dissociation rate constant was calculated (3.42 x 10(-3) to 4.50 x 10(-3) s(-1)). The chondrocyte-derived species was found to prevent collagenolytic cleavage of type I collagen and to stimulate the rate of type I collagen fibril formation in a concentration-dependent manner. By contrast, the cartilage major form had an inhibitory effect on type I collagen fibrillogenesis. Digestion with N-glycosidase F, endoglycosidase H and lectin blotting did not reveal any difference in the carbohydrate component of these two YKL-40 species, indicating that this does not account for the opposing effects on fibril formation rate.
Bigg
Heather F
HF
Musculoskeletal Research Group, Catherine Cookson Building, The Medical School, Framlington Place, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne NE2 4HH, United Kingdom. Electronic address: Heather.Bigg@ncl.ac.uk.
Wait
Robin
R
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1, Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom.
Rowan
Andrew D
AD
Musculoskeletal Research Group, Catherine Cookson Building, The Medical School, Framlington Place, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
Cawston
Tim E
TE
Musculoskeletal Research Group, Catherine Cookson Building, The Medical School, Framlington Place, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne NE2 4HH, United Kingdom.
D054392:Adipokines; D000595:Amino Acid Sequence; D000818:Animals; D002356:Cartilage / Q000378:metabolism; D002417:Cattle; D000071451:Chitinase-3-Like Protein 1; D019902:Chondrocytes / Q000378:metabolism; D024042:Collagen Type I / Q000737:chemistry*; D024022:Fibrillar Collagens / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000737:chemistry; D037102:Lectins / Q000737:chemistry*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D008969:Molecular Sequence Data; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000737:chemistry; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D024042:Collagen Type I; D024022:Fibrillar Collagens; D006023:Glycoproteins; D037102:Lectins; D019716:Tissue Inhibitor of Metalloproteinase-2; D006026:Glycoside Hydrolases; D020781:Matrix Metalloproteinase 1; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase