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Tytuł pozycji:

Salinomycin alleviates osteoarthritis progression via inhibiting Wnt/β-catenin signaling.

Tytuł:
Salinomycin alleviates osteoarthritis progression via inhibiting Wnt/β-catenin signaling.
Autorzy:
Chen J; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China; The First People's Hospital of Zhaoqing, Zhaoqing 526020, China.
Liu J; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Chen S; Guangxi Botanical Garden of Medicinal Plants, Nanning, China; Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Lai R; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Zheng C; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Lu J; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Jiang X; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
He F; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Yang C; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Li K; Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Xie K; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Tang Y; Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China. Electronic address: .
Wang L; State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai, China.
Źródło:
International immunopharmacology [Int Immunopharmacol] 2022 Nov; Vol. 112, pp. 109225. Date of Electronic Publication: 2022 Sep 09.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
MeSH Terms:
Osteoarthritis*/metabolism
Osteoarthritis*/pathology
Osteophyte*/metabolism
Osteophyte*/pathology
Wnt Signaling Pathway*
Animals ; Mice ; Aggrecans/metabolism ; beta Catenin/metabolism ; Cartilage, Articular/pathology ; Cells, Cultured ; Chondrocytes ; Disease Models, Animal ; Interleukin-1beta/metabolism ; Ionophores/metabolism ; Ionophores/pharmacology ; Ionophores/therapeutic use ; Matrix Metalloproteinase 13/metabolism ; Menisci, Tibial/pathology ; Sclerosis/metabolism ; Sclerosis/pathology ; Thrombospondins/metabolism ; Thrombospondins/pharmacology ; Thrombospondins/therapeutic use
Contributed Indexing:
Keywords: IL-1β; Osteoarthritis; Phosphorylated Lrp6; Salinomycin; Wnt/β-catenin signaling
Substance Nomenclature:
0 (Aggrecans)
0 (beta Catenin)
0 (Interleukin-1beta)
0 (Ionophores)
EC 3.4.24.- (Matrix Metalloproteinase 13)
62UXS86T64 (salinomycin)
0 (Thrombospondins)
Entry Date(s):
Date Created: 20220912 Date Completed: 20221024 Latest Revision: 20221024
Update Code:
20240104
DOI:
10.1016/j.intimp.2022.109225
PMID:
36095950
Czasopismo naukowe
Osteoarthritis (OA) is the most prevalent degenerative whole-joint disease characterized by cartilage degeneration, synovial hyperplasia, osteophyte formation, and subchondral bone sclerosis. Currently there are no disease-modifying treatments available for OA because its etiology and pathogenesis are largely unknown. Here we report that a natural carboxylic polyether ionophore that is used as an anti-tumor drug, salinomycin (SAL), may be a promising therapeutic drug for OA in the future. We found that SAL showed no cytotoxicity on mouse chondrocytes and displayed a protective effect against interleukin-1β (IL-1β), in cultured mouse chondrocytes and cartilage explants. Treatment with low SAL concentrations directly upregulated the anabolism factors collagen II and aggrecan, while it inhibited the catabolic factors matrix metalloproteinase-13 (MMP13) and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) to protect against extracellular matrix (ECM) degradation, and also suppressed inflammatory responses in mouse chondrocytes. Furthermore, SAL reduced the severity of OA-associated changes and delayed cartilage destruction, subchondral bone sclerosis, and osteophyte formation in a destabilized medial meniscus (DMM) surgery-induced mouse OA model. Mechanistically, a low SAL concentration induced anabolism and inhibited catabolism in chondrocytes via inhibiting Lrp6 phosphorylation and Wnt/β-catenin signaling. Our results suggested that SAL may serve as a potential disease-modifying therapeutic against OA pathogenesis.
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 © 2022. Published by Elsevier B.V.)

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