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

抄録

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 alpha 9b1 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.

収録刊行物

• PLOS one

  PLOS one 9 (12), e116210-, 2014-12-29

  Public Library of Science

詳細情報

• CRID: 1050564288971418496
• NII論文ID: 120005540287
• HANDLE: 2115/57930
• ISSN: 19326203
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles