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

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 matri...

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Autores principales: Kon, Shigeyuki, Nakayama, Yosuke, Matsumoto, Naoki, Ito, Koyu, Kanayama, Masashi, Kimura, Chiemi, Kouro, Hitomi, Ashitomi, Dai, Matsuda, Tadashi, Uede, Toshimitsu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278882/
https://www.ncbi.nlm.nih.gov/pubmed/25545242
http://dx.doi.org/10.1371/journal.pone.0116210
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author Kon, Shigeyuki
Nakayama, Yosuke
Matsumoto, Naoki
Ito, Koyu
Kanayama, Masashi
Kimura, Chiemi
Kouro, Hitomi
Ashitomi, Dai
Matsuda, Tadashi
Uede, Toshimitsu
author_facet Kon, Shigeyuki
Nakayama, Yosuke
Matsumoto, Naoki
Ito, Koyu
Kanayama, Masashi
Kimura, Chiemi
Kouro, Hitomi
Ashitomi, Dai
Matsuda, Tadashi
Uede, Toshimitsu
author_sort Kon, Shigeyuki
collection PubMed
description 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.
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spelling pubmed-42788822015-01-05 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 Kon, Shigeyuki Nakayama, Yosuke Matsumoto, Naoki Ito, Koyu Kanayama, Masashi Kimura, Chiemi Kouro, Hitomi Ashitomi, Dai Matsuda, Tadashi Uede, Toshimitsu PLoS One Research Article 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. Public Library of Science 2014-12-29 /pmc/articles/PMC4278882/ /pubmed/25545242 http://dx.doi.org/10.1371/journal.pone.0116210 Text en © 2014 Kon et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kon, Shigeyuki
Nakayama, Yosuke
Matsumoto, Naoki
Ito, Koyu
Kanayama, Masashi
Kimura, Chiemi
Kouro, Hitomi
Ashitomi, Dai
Matsuda, Tadashi
Uede, Toshimitsu
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278882/
https://www.ncbi.nlm.nih.gov/pubmed/25545242
http://dx.doi.org/10.1371/journal.pone.0116210
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