Suramin ameliorates osteoarthritis by acting on the Nrf2/HO-1 and NF-κB signaling pathways in chondrocytes and promoting M2 polarization in macrophages.

Autor: Shen PC; Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan; Department of Orthopedics, Faculty of Medical School, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan., Huang SH; Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan., Liu ZM; Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan., Lu CC; Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan; Department of Orthopedics, Faculty of Medical School, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan; Department of Orthopaedic Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan; Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan., Chou SH; Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan., Tien YC; Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan; Department of Orthopedics, Faculty of Medical School, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan. Electronic address: chondrocyte@yahoo.com.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Jul; Vol. 120, pp. 110295. Date of Electronic Publication: 2023 May 12.
DOI: 10.1016/j.intimp.2023.110295
Abstrakt: Osteoarthritis (OA)-the most prevalent of arthritis diseases-is a complicated pathogenesis caused by cartilage degeneration and synovial inflammation. Suramin has been reported to enhance chondrogenic differentiation. However, the therapeutic effect of suramin on OA-induced cartilage destruction has remained unclear. Suramin is an anti-parasitic drug that has potent anti-purinergic properties. This study investigated the protective effects and underlying mechanisms of suramin on articular cartilage degradation using an in vitro study and mice model with post-traumatic OA. We found that suramin markedly suppressed the IL-1β increased expression of matrix destruction proteases-such as ADAMT4, ADAMTS5, MMP3, MMP13, and inflammatory mediators-including the iNOS, COX2, TNFα, and IL-1β; while greatly enhancing the synthesis of cartilage anabolic factors-such as COL2A1, Aggrecan and SOX9 in IL-1β-induced porcine chondrocytes. In vivo experiments showed that intra-articular injection of suramin ameliorated cartilage degeneration and inhibited synovial inflammation in an anterior cruciate ligament transection (ACLT)-induced OA mouse model. In mechanistic studies, we found that exogenous supplementation of suramin can activate Nrf2, and accordingly inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) and mitogen-activated protein kinase (MAPK) pathways, thereby alleviating the inflammation and ECM degeneration of chondrocytes stimulated by IL-1β. In addition, suramin also repolarized M1 macrophages to the M2 phenotype, further reducing the apoptosis of chondrocytes. Collectively, the results of the study suggests that suramin is a potential drugs which could serve as a facilitating drug for the application of OA therapy toward clinical treatment.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: