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

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

  • Int Immunopharmacol. 2023 May 12;120:110295. doi: 10.1016/j.intimp.2023.110295.
Po-Chih Shen 1,  Shih-Hao Huang 2,  Zi-Miao Liu 2,  Cheng-Chang Lu 3,  Shih-Hsiang Chou 2,  Yin-Chun Tien 4
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 80708, Taiwan.
  • 3 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.
  • 4 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.
PMID: 37182454 DOI: 10.1016/j.intimp.2023.110295
Abstract

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.

Keywords

Macrophage polarization; Nrf2/HO-1; OA; Suramin.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z