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

Shigeyuki Kon; Yosuke Nakayama; Naoki Matsumoto; Koyu Ito; Masashi Kanayama; Chiemi Kimura; Hitomi Kouro; Dai Ashitomi; Tadashi Matsuda; Toshimitsu Uede

doi:10.1371/journal.pone.0116210

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

Shigeyuki Kon, Yosuke Nakayama, Naoki Matsumoto, Koyu Ito, Masashi Kanayama, Chiemi Kimura, Hitomi Kouro, Dai Ashitomi, Tadashi Matsuda, Toshimitsu Uede

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

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.

Original language	English
Article number	e116210
Journal	PloS one
Volume	9
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0116210
Publication status	Published - 2014 Dec 29
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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Kon, S., Nakayama, Y., Matsumoto, N., Ito, K., Kanayama, M., Kimura, C., Kouro, H., Ashitomi, D., Matsuda, T., & Uede, T. (2014). 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. PloS one, 9(12), [e116210]. https://doi.org/10.1371/journal.pone.0116210

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 et al.
In: PloS one, Vol. 9, No. 12, e116210, 29.12.2014.

Research output: Contribution to journal › Article › peer-review

Kon, S, Nakayama, Y, Matsumoto, N, Ito, K, Kanayama, M, Kimura, C, Kouro, H, Ashitomi, D, Matsuda, T & Uede, T 2014, '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', PloS one, vol. 9, no. 12, e116210. https://doi.org/10.1371/journal.pone.0116210

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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.",

author = "Shigeyuki Kon and Yosuke Nakayama and Naoki Matsumoto and Koyu Ito and Masashi Kanayama and Chiemi Kimura and Hitomi Kouro and Dai Ashitomi and Tadashi Matsuda and Toshimitsu Uede",

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AU - Ito, Koyu

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AU - Kimura, Chiemi

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AU - Matsuda, Tadashi

AU - Uede, Toshimitsu

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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

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