| Autor: |
Kaihu Li, Yong Zhu, Penghui Zhang, Mauro Alini, Sibylle Grad, Zhen Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal of Orthopaedic Translation, Vol 38, Iss , Pp 106-116 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2214-031X |
| DOI: |
10.1016/j.jot.2022.10.003 |
| Popis: |
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 in vitro (chondrocyte pellets) and ex vivo (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 (IL-6), and cyclooxygenase-2 (COX-2) while upregulating proteoglycan 4 (PRG4) and cartilage oligomeric matrix protein (COMP) 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 in vitro and ex vivo human inflammatory OA models, showing its translational potential for OA treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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