Regular Article
Effects of Thrombospondin-1 on Disease Course and Angiogenesis in Rat Adjuvant-Induced Arthritis

https://doi.org/10.1006/clin.1997.4480Get rights and content

Abstract

Leukocyte extravasation into the synovium is important in rheumatoid arthritis (RA). Thrombospondin (TSP)-1 mediates cell adhesion and migration and inhibits angiogenesis, and it has been implicated in RA. However, little information is available on the role of TSP-1 in arthritis-associated inflammation and neovascularization. Therefore, we analyzed the effects of TSP-1 in adjuvant-induced arthritis (AIA), a rat model for RA. Hydron pellets containing TSP-1 were implanted in one ankle of AIA rats post-adjuvant injection, while the contralateral ankle received sham implants. Body weight loss and joint swelling were determined in comparison to nonimplanted AIA controls. In addition, synovial vessel counts were obtained in TSP-1-versus sham-implanted ankles of the same rat. The implantation of TSP-1 pellets into one ankle resulted in an enhancement of swelling in both ankles. Furthermore, TSP-1 exhibited a biphasic modulatory effect on synovial vessel counts (P< 0.05). In conclusion, TSP-1 implanted into one ankle of AIA rats may augment the severity of the disease. One possible explanation, among others, for the modulating effect of TSP-1 on inflammation may be its effect on arthritis-related angiogenesis.

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    This work was supported by NIH Grants AR-30692 (A.E.K. and C.B.L.) and AR-41492 (A.E.K.), funds from the Veterans’ Administration Research Service (A.E.K.), the Dr. Ralph and Marion Falk Challenge Prize of the Arthritis Foundation, Illinois Chapter (A.E.K.), Hungarian Scientific Foundation Grant No. T013239 (Z.S.), and Hungarian Medical Research Council Grant 156/93 (Z.S.)

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