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MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain

Pain is the hallmark symptom of osteoarthritis (OA), and current analgesic treatments may be insufficient or have potentially adverse effects. The inhibition of Monoacylglycerol lipase (MAGL) produces anti-inflammatory and anti-nociceptive effects. However, the potential mechanism of MAGL in OA pain...

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Autores principales: Gu, Chengyong, Chen, Mo, Li, Xueyan, Geng, Dechun, Wang, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10172810/
https://www.ncbi.nlm.nih.gov/pubmed/37144506
http://dx.doi.org/10.3892/mmr.2023.13004
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author Gu, Chengyong
Chen, Mo
Li, Xueyan
Geng, Dechun
Wang, Chen
author_facet Gu, Chengyong
Chen, Mo
Li, Xueyan
Geng, Dechun
Wang, Chen
author_sort Gu, Chengyong
collection PubMed
description Pain is the hallmark symptom of osteoarthritis (OA), and current analgesic treatments may be insufficient or have potentially adverse effects. The inhibition of Monoacylglycerol lipase (MAGL) produces anti-inflammatory and anti-nociceptive effects. However, the potential mechanism of MAGL in OA pain remains unclear. In the present study, the synovial tissues were removed from OA patients and mice. Immunohistochemical staining and western blotting were used to detect the expression of MAGL. M1 and M2 polarization markers were detected by flow cytometry and western blotting, and the mitophagy levels were detected by the immunofluorescence staining of mitochondrial autophagosomes with lysosomes and western blotting. The OA mice were intraperitoneally injected with MJN110 to inhibit MAGL once a day for a week. Mechanical and thermal pain thresholds were detected by electronic Von Frey and hot plate methods on days 0, 3, 7, 10, 14, 17, 21, and 28. The accumulation of MAGL in the synovial tissues of OA patients and mice promoted the polarization of macrophages towards an M1 phenotype. Pharmacological inhibition and siRNA knockdown of MAGL promoted polarization of M1 macrophages towards an M2 phenotype. MAGL inhibition increased the mechanical and thermal pain thresholds of OA mice and enhanced the mitophagy levels of M1 macrophages. In conclusion, in the present study, it was shown that MAGL regulated synovial macrophage polarization by inhibiting mitophagy in OA.
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spelling pubmed-101728102023-05-12 MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain Gu, Chengyong Chen, Mo Li, Xueyan Geng, Dechun Wang, Chen Mol Med Rep Articles Pain is the hallmark symptom of osteoarthritis (OA), and current analgesic treatments may be insufficient or have potentially adverse effects. The inhibition of Monoacylglycerol lipase (MAGL) produces anti-inflammatory and anti-nociceptive effects. However, the potential mechanism of MAGL in OA pain remains unclear. In the present study, the synovial tissues were removed from OA patients and mice. Immunohistochemical staining and western blotting were used to detect the expression of MAGL. M1 and M2 polarization markers were detected by flow cytometry and western blotting, and the mitophagy levels were detected by the immunofluorescence staining of mitochondrial autophagosomes with lysosomes and western blotting. The OA mice were intraperitoneally injected with MJN110 to inhibit MAGL once a day for a week. Mechanical and thermal pain thresholds were detected by electronic Von Frey and hot plate methods on days 0, 3, 7, 10, 14, 17, 21, and 28. The accumulation of MAGL in the synovial tissues of OA patients and mice promoted the polarization of macrophages towards an M1 phenotype. Pharmacological inhibition and siRNA knockdown of MAGL promoted polarization of M1 macrophages towards an M2 phenotype. MAGL inhibition increased the mechanical and thermal pain thresholds of OA mice and enhanced the mitophagy levels of M1 macrophages. In conclusion, in the present study, it was shown that MAGL regulated synovial macrophage polarization by inhibiting mitophagy in OA. D.A. Spandidos 2023-05-02 /pmc/articles/PMC10172810/ /pubmed/37144506 http://dx.doi.org/10.3892/mmr.2023.13004 Text en Copyright: © Gu et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Gu, Chengyong
Chen, Mo
Li, Xueyan
Geng, Dechun
Wang, Chen
MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain
title MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain
title_full MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain
title_fullStr MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain
title_full_unstemmed MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain
title_short MAGL regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain
title_sort magl regulates synovial macrophage polarization vis inhibition of mitophagy in osteoarthritic pain
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10172810/
https://www.ncbi.nlm.nih.gov/pubmed/37144506
http://dx.doi.org/10.3892/mmr.2023.13004
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