Anti-inflammatory and pro-anabolic effects of 5-aminosalicylic acid on human inflammatory osteoarthritis models.

Background: Osteoarthritis (OA) is the most common degenerative joint disease, mainly affecting the elderly worldwide, for which the drug treatment remains a major challenge. Low-grade inflammation plays a pivotal role in OA onset and progression. Exploration of notable anti-inflammatory and disease-modifying drugs on human samples could facilitate the evaluation of therapeutic strategies for OA.

Methods: The anti-inflammatory drug 5-aminosalicylic acid (5-ASA) is a first-line drug for ulcerative colitis (UC), however no study has explored the effects of 5-ASA on articular chondrocytes. In this work, both (chondrocyte pellets) and (osteochondral explants) human inflammatory OA models were applied to evaluate the effects of 5-ASA.

Results: In the inflammatory pellet model, 5-ASA remarkably downregulated the gene expression of interleukin-6 (), and cyclooxygenase-2 () while upregulating proteoglycan 4 () and cartilage oligomeric matrix protein () gene expression. Total glycosaminoglycan (GAG) synthesis by pellets was markedly increased in 5-ASA-treated groups compared with the inflammatory group. In conditioned medium, inflammatory mediators (IL-8, nitric oxide) were markedly inhibited upon 5-ASA treatment. Moreover, histological staining showed 5-ASA retained proteoglycan content and inhibited degradation of extracellular matrix (ECM) core components, aggrecan (ACAN) and collagen type II (COL2). In the inflammatory explant model, 5-ASA mitigated signs of OA development by reducing inflammatory mediators and GAG loss.

Conclusions: These findings suggest that 5-ASA has anti-inflammatory and pro-anabolic effects on human chondrocyte pellet and osteochondral explant inflammatory OA models.

The Translational Potential Of This Article: Disease-modifying OA drugs are an unmet clinical need for the treatment of OA. Our study explored and demonstrated the anti-inflammatory and protective effects of 5-ASA on and human inflammatory OA models, showing its translational potential for OA treatment.