ABSTRACT. Aseptic loosening associated with wear particle-induced inflammation is a major cause of joint implant failure. Recent studies have demonstrated the therapeutic effects of p38 mitogen-activated protein kinase (MAPK)-based therapies on chronic inflammatory diseases. The purpose of this study was to investigate whether SB203580, a p38 MAPK inhibitor, inhibits wear debris-induced inflammatory osteolysis in mice through downregulation of receptor activator of nuclear factor kβ (RANK)/RANK ligand (RANKL). We used a murine osteolysis model to study the effect of SB203580 on RANKL/RANK signaling and titanium particle-induced osteolysis in vivo. Pouch membranes p38 inhibitor on wear debris-induced inflammatory osteolysis with intact bone implants were analyzed using histological analysis and transmission electron microscopy, and the levels of RANK and RANKL protein and mRNA were evaluated by immunohistological staining and real-time reverse transcriptase-polymerase chain reaction. SB203580 had less of an effect on RANK and RANKL expression under wear debris-induced conditions. The number of TRAP-positive cells was remarkably reduced in Ti-particle-induced pouch tissues. These effects were confirmed through the transmission electron microscopy results. These results suggest that p38 MAPK-based therapies are beneficial in preventing aseptic loosening associated with total joint replacement by modulating RANK-RANKL signaling.
MSCs have been proven to have immune modulation and anti-inflammation capabilities, but the mechanisms are still under investigation. Recently, oxylipins have been identified to be involved in the immuno-regulation function of MSCs. In the present research, we employed a newly developed UPLC-MS/MS method to identify and quantify the oxylipin profile of ADSCs under proinflammatory stimulation (TNF-α and IFN-𝛾). As a result, among the analyzed 71 oxylipins, we detected and quantified 49 oxylipins derived from six major n-6 and n-3 polyunsaturated fatty acids (PUFAs) including arachidonic (AA), linoleic (LA), alpha-linolenic (ALA), dihomo-𝛾-linolenic acid (DGLA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids in all samples, while 4 oxylipins were detected only in a part of samples and 18 were not detected in all samples. Nine oxylipins were found to be significantly differentially produced in ADSCs after 24 hours of inflammatory stimulation, among which, several oxylipins were reported to be having anti-inflammation or proresolving functions and involved in lipid mediator switching. The results reported here make a fundamental step towards a comprehensive characterization of MSCs derived oxylipins as potential modulators of inflammation and immunoreaction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.