Article ; Online: Atractylenolide-III attenuates osteoarthritis by repolarizing macrophages through inactivating TLR4/NF-κB signaling.
International immunopharmacology
2024 Volume 129, Page(s) 111629
Abstract: Background: As a common chronic musculoskeletal condition, osteoarthritis (OA) presently lacks particular treatment strategies. The aim of this study was to examine how AT-III therapies affected macrophage repolarity in order to slow down the ... ...
| Abstract | Background: As a common chronic musculoskeletal condition, osteoarthritis (OA) presently lacks particular treatment strategies. The aim of this study was to examine how AT-III therapies affected macrophage repolarity in order to slow down the advancement of OA. Methods: RAW264.7 macrophages were polarized to M1 subtypes then administered with different concentrations of AT-III. Immunofluorescence, qRT-PCR and flow cytometry were used to assess the polarization of the macrophages. The mechanism of AT-III repolarize macrophages was evaluated by western blot. Furthermore, the effects of macrophage conditioned media (CM) on the migration, proliferation, and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were investigated using CCK-8 assays, the scratch test, and alcian blue staining. The effects of macrophage CM on chondrocyte proliferation and degeneration were investigated using CCK-8 and qRT-PCR. In vivo micro-CT and histological observations were performed on rats with anterior cruciate ligament transection and partial medial meniscectomy, either with or without AT-III treatment. Results: AT-III repolarized M1 macrophages to M2 phenotype. Mechanistically, AT-III reduced the expression of Toll-like receptor(TLR) 4 induced by lipopolysaccharide in RAW264.7 and lowered nuclear factor-κB (NF-κB) signaling molecules p-p65 and p-IκBα. The TLR4 agonist RS09 reversed the effects of AT-III on macrophage repolarization. AT-III-induced macrophages CM stimulated BMSCs migration, proliferation and chondrogenic differentiation. AT-III-treated macrophage CM promoted chondrocyte proliferation while inhibiting chondrocyte degeneration. In vivo, AT-III treatment alleviated the degree of synovitis, inhibited subchondral bone remodeling and reduced cartilage destruction in the rat OA model. Conclusions: AT-III attenuates OA by repolarizing macrophages through inactivating TLR4/NF-κB signaling. These data suggest that AT-III may be an effective therapeutic candidate for OA treatment. |
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| MeSH term(s) | Rats ; Animals ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; Sincalide/metabolism ; Sincalide/pharmacology ; Sincalide/therapeutic use ; Macrophages ; Osteoarthritis/drug therapy ; Osteoarthritis/metabolism |
| Chemical Substances | NF-kappa B ; Toll-Like Receptor 4 ; Sincalide (M03GIQ7Z6P) |
| Language | English |
| Publishing date | 2024-02-11 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 2043785-7 |
| ISSN | 1878-1705 ; 1567-5769 |
| ISSN (online) | 1878-1705 |
| ISSN | 1567-5769 |
| DOI | 10.1016/j.intimp.2024.111629 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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