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The importance of Synoviolin in embryogenesis

Rheumatoid arthritis (RA) is one of the most critical articular diseases with synovial hyperplasia followed by impairment of quality of life. However, the mechanism(s) that regulates synovial cell outgrowth is not fully understood.

To clarify its mechanism(s), we carried out immunoscreening using antirheumatoid synovial cell antibody, and cloned 'Synoviolin'. Synoviolin was highly expressed in the rheumatoid synovium, and mice overexpressing this molecule developed spontaneous arthropathy. Thus, it was demonstrated that Synoviolin is a novel pathogenic factor for arthropathy.

In this study, to understand the physiological role of Synoviolin in vivo, we generated synoviolin-deficient (syno-/-) mice by gene-targeted disruption. Surprisingly, all fetuses lacking synoviolin died in utero by embryonic day 12.5–13.5. Histologically, syno-/- embryos showed generalized low cellular density and aberrant apoptosis. In the hematopoietic system, apoptosis, nuclear fragmentation of erythroblasts, Howell–Jolly body formation and hemophagocytosis were observed. These results indicate that lack of Synoviolin is associated with abnormal erythroid differentiation caused by augmentation of apoptosis, and it was probable that syno-/- embryos died of anemia as a result of a reduced number of circulating erythroblasts.

In conclusion, Synoviolin has an anti-apoptotic effect, and is essential for embryogenesis. For further study, clearing the molecular mechanism of Synoviolin in apoptosis could lead to cure of RA.

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Yagishita, N., Amano, T., Yamasaki, S. et al. The importance of Synoviolin in embryogenesis. Arthritis Res Ther 5 (Suppl 3), 143 (2003).

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