[HTML][HTML] Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis

N Yamamoto, F Sakai, S Kon… - The Journal of …, 2003 - Am Soc Clin Investig
N Yamamoto, F Sakai, S Kon, J Morimoto, C Kimura, H Yamazaki, I Okazaki, N Seki, T Fujii…
The Journal of clinical investigation, 2003Am Soc Clin Investig
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 α9 and α4 integrins. Since cleavage of OPN by thrombin exposes the
cryptic epitope recognized by α9 and α4 integrins, we investigated the role of the cryptic …
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 α9 and α4 integrins. Since cleavage of OPN by thrombin exposes the cryptic epitope recognized by α9 and α4 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.
The Journal of Clinical Investigation