| Literature DB >> 12865407 |
Nobuchika Yamamoto1, Fumihiko Sakai, Shigeyuki Kon, Junko Morimoto, Chiemi Kimura, Harumi Yamazaki, Ikuko Okazaki, Nobuo Seki, Takashi Fujii, Toshimitsu Uede.
Abstract
It has been shown that osteopontin (OPN) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). However, the molecular mechanism of OPN action is yet to be elucidated. Splenic monocytes obtained from arthritic mice exhibited a significant capacity for cell migration toward thrombin-cleaved OPN but not toward full-length OPN. Migratory monocytes expressed alpha9 and alpha4 integrins. Since cleavage of OPN by thrombin exposes the cryptic epitope recognized by alpha9 and alpha4 integrins, we investigated the role of the cryptic epitope SLAYGLR in a murine RA model by using a specific antibody (M5) reacting to SLAYGLR sequence. The M5 antibody could abrogate monocyte migration toward the thrombin-cleaved form of OPN. Importantly, M5 antibody could inhibit the proliferation of synovium, bone erosion, and inflammatory cell infiltration in arthritic joints. Thus, we demonstrated that a cryptic epitope, the SLAYGLR sequence of murine OPN, is critically involved in the pathogenesis of a murine model of RA.Entities:
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Year: 2003 PMID： 12865407 PMCID： PMC164290 DOI： 10.1172/JCI17778
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808