TEMPORAL EVALUATION OF SYNOVIAL REMODELING AND INFLAMMATORY PROCESS IN mBSA/CFA-INDUCED ARTHRITIS

• Grant number: 24/23736-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Walcy Paganelli Rosolia Teodoro
• Grantee: Sarah Romaniw Raymundo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.5% to 1% of the world population, being more prevalent in women, with genetic and environmental factors involved in its pathogenesis. The synovium, which lines the synovial joints, is the most affected tissue, presenting hyperplasia, cellular infiltration and tissue destruction. The synovial membrane is composed of type A and B synoviocytes, which favor the formation of pannus, which degrades adjacent cartilage and bone. This process induces changes in the synovial extracellular matrix (ECM), composed mainly of types I, III and V collagen, fibronectin and proteoglycans. The imbalance in collagen metabolism favors the invasion of pannus and the progression of fibrosis, resulting in deformities and functional disability. Among the changes in collagen during synovial remodeling, the increase in type V collagen (ColV) stands out. ColV is currently considered a sequestered antigen, and its importance in autoimmunity has been demonstrated in several pathological processes. On the other hand, the induction of oral or nasal tolerance with ColV has been shown to be effective in inhibiting these processes in preclinical models. We recently demonstrated that after 30 days of induction of monoarthritis by methylated albumin, there is pannus formation, characterized mainly by an increase in lymphocytes and macrophages, immersed in a large amount of ColV, in addition to intense synovial remodeling and the presence of anti-collagen V antibodies in the serum. These data indicate that synovial remodeling, resulting from induced arthritis in animals, can interfere with the constitution and distribution of the extracellular matrix (ECM), exposing antigenic epitopes of collagen V, which would stimulate a cellular and humoral response, contributing to inflammation in arthritis. At present, it is not yet completely clear how the increase in ColV occurs among inflammatory cells and what its relationship is with synovial remodeling in arthritis. Furthermore, it is not known whether the increased proportion of ColV could interfere with the fibrillogenesis of Col I and III or with the function of proteoglycans involved in collagen synthesis, such as decorin. Understanding these processes is essential for the development of new therapies that can protect joint components, helping to improve the quality of life of patients with arthritis. (AU)