Amelioration of inflammation, angiogenesis and CTGF expression in an arthritis model by a TSP1-derived peptide treatment

Objective: To evaluate the effect of a thrombosponclin I (TSI) +derived pepticle on inflammation and angiogenesis in an animal model of erosive arthritis and to assess the relationship between TSP I and connective tissue growth factor (CTGF) in the pathophysiology of rheumatoid arthritis. Methods: Erosive arthritis in Lewis rats was induced by pepticloglycan-polysaccharicle (PG-PS). Animals were divided into fourgroups: (1) negative control and groups receiving, (2) no treatment, (3) treatmentwith a TSPI-derived pepticle, and (4) treatment with a scrambled pepticle. Samples obtained from ankle joint, spleen and liver were studied using histology, histomorphometry, immunohistochemistry and RT-PCR. Results: Histological data indicated that the TSPI-derived pepticle treatment decreased neovascularization, leukocyte infiltration and thickening of the synovial lining of the joint, and reduced granuloma formation in the spleen and liver when compared to control groups. Higher concentrations of CTGF and TSP I proteins were observed in the affected areas of animals which did not receive TSPI-derived pepticle treatment. Also, immunofluorescence and RT-PCR analyses showed an increase in CTGF protein expression and regulation, respectively, in the tissues of untreated animals when compared to the TSPI-derived pepticle treated animals. By immunofluorescence, TSPI expression was decreased in the TSPI-derived peptide treated animals. Moreover, macrophage/monocyte-specific staining revealed a decrease in cell infiltration in the articular tissue of the TSPI-derived pepticle treated animals. Conclusion: Both inflammation and angiogenesis were decreased after TSPI-derived pepticle treatment indicating a potential pathway by which TSPI interaction with neutrophils induces CTGF in RA affected tissues.