EVALUATION OF MACROPHAGE POLARIZATION BY MONOMETHYL FUMARATE ASSOCIATED WITH HYDROGEL IN EXPERIMENTAL OSTEOARTHRITIS: CARTILAGE REGENERATION AND PAIN REDUCTION.

• Grant number: 24/15024-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2025
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Carlos Amilcar Parada
• Grantee: Douglas Menezes de Souza
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Osteoarthritis (OA) is a chronic disease associated with degenerating joint structures (cartilage), resulting in hypertrophic changes in bones, formation of osteophytes, synovial inflammation, and pain. In the progression of OA, the exacerbated increase in pro-inflammatory macrophages (M1) is associated with chondrocyte mortality, degradation of the extracellular matrix, and exposure of the subchondral bone leading to pain. Currently, pharmacological treatments for OA are still limited in reducing pain and have considerable side effects related to prolonged use, in addition to favoring the degeneration of joint tissues (local use). Thus, disease-modifying medications (DMARDs) have emerged as an alternative to the control of OA. Among these drugs, we intend to evaluate monomethyl fumarate (MMF) to modulate the inflammatory response through the polarization of type 1 macrophages into type 2, since a balance between these cells can induce analgesia and favor tissue regeneration. Therefore, the objectives of this work: 1. to evaluate whether MMF associated with hydrogel intra-articularly promotes the modulation of the inflammatory response, analgesia, and cartilage regeneration correlated with the polarization of macrophages in experimental osteoarthritis (OAE) induced by the application of mono iodine acetate (MIA) in the knee of rats. 2. Evaluate the polarization of macrophages induced by MMF in co-culture of human macrophages and chondrocytes 3. Carry out a preliminary clinical study in humans with OA treated with intra-articular application of MMF associated with the hydrogel and evaluate the presence of cytokines in the synovial fluid pro- and anti-inflammatory and markers of type 1 and type 2 macrophages. (AU)