title: A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for α9β1 integrin is involved in the anti-type II collagen antibody-induced arthritis.
abstract: Osteopontin (OPN) is a multifunctional protein that has been linked to various intractable inflammatory diseases. One way by which OPN induces inflammation is the production of various functional fragments by enzyme cleavage. It has been well appreciated that OPN is cleaved by thrombin, and/or matrix metalloproteinase-3 and -7 (MMP-3/7). Although the function of thrombin-cleaved OPN is well characterized, little is known about the function of MMP-3/7-cleaved OPN. In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Koyu
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanayama
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Kimura
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kouro
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Ashitomi
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.affiliation: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D016466:CHO Cells; D002465:Cell Movement / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D053495:Osteopontin / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000906:Antibodies; D024043:Collagen Type II; D016023:Integrins; D008024:Ligands; D010455:Peptides; C113256:integrin alpha 9 beta 1; D053495:Osteopontin; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7