Avaliação do papel da proteína Anexina A1 na inflamação, lesão e disfunção tecidual da osteoartrite experimental

Abstract

Osteoarthritis (OA) is a chronic and debilitating disease that affects a large portion of the global population, with higher prevalence among the elderly. Inflammation and structural damage in OA are progressive and associated with both genetic and environmental factors, such as biomechanical stress. However, current therapeutic options remain ineffective in preventing disease progression. At present, available pharmacological treatments for OA are mostly limited to symptom management, particularly pain relief. It is therefore speculated that future disease-modifying drugs may act by regulating the activity of synovial cells. In this study, we propose that Annexin A1, a potent molecule involved in the resolution of inflammation, may help control joint damage in OA. Using an experimental model, we found that Annexin A1-deficient mice exhibited worsened osteoarthritis, showing increased pain and joint damage compared to wild-type animals. Interestingly, mice treated with the Annexin A1 mimetic peptide Ac2-26 displayed reduced lesion progression and pain in experimental OA, even when treatment was initiated at later stages. Furthermore, treatment improved MMP-3 levels, and similarly, RANK-L analysis—a parameter of joint injury—also showed a reduction following treatment. Finally, IL-10 levels were elevated after treatment. These findings suggest a promising role for Annexin A1 and its mimetic peptide Ac2-26 in mitigating joint damage and alleviating symptoms associated with OA.