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Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis
Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor ant...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10505157/ https://www.ncbi.nlm.nih.gov/pubmed/37717108 http://dx.doi.org/10.1038/s41598-023-42673-2 |
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author | Nekomoto, Akinori Nakasa, Tomoyuki Ikuta, Yasunari Ding, Chenyang Miyaki, Shigeru Adachi, Nobuo |
author_facet | Nekomoto, Akinori Nakasa, Tomoyuki Ikuta, Yasunari Ding, Chenyang Miyaki, Shigeru Adachi, Nobuo |
author_sort | Nekomoto, Akinori |
collection | PubMed |
description | Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor antagonist (rimegepant) could suppress OA progression and relieve pain in two OA models. C57BL/6 mice (10-week-old) underwent surgical destabilization of the medial meniscus, and Rimegepant (1.0 mg/kg/100 μL) or phosphate-buffered saline (100 μL) was administered weekly intraperitoneally after OA surgery and evaluated at 4, 8, and 12 weeks. In the senescence-accelerated mice (SAM)-prone 8 (SAMP8), rimegepant was administered weekly before and after subchondral bone sclerosis and sacrificed at 9 and 23 weeks, respectively. Behavioral assessment and immunohistochemical staining (CGRP) of the dorsal root ganglion (DRG) were conducted to assess pain. In DMM mice, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed in the rimegepant group. In SAMP8, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed by rimegepant at 9 weeks; however, not at 23 weeks. Behavioral assessment shows the traveled distance and the number of standings in the rimegepant group were significantly longer and higher. In addition, CGRP expression of the DRG was significantly lower in the rimegepant group at 8 and 12 weeks of DMM and 9 weeks of SAMP8 treatment. No adverse effects were observed in either of the mouse models. Inhibition of CGRP signaling has the potential to be a therapeutic target to prevent OA progression and suppress pain through the attenuation of subchondral bone sclerosis and synovitis. |
format | Online Article Text |
id | pubmed-10505157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105051572023-09-18 Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis Nekomoto, Akinori Nakasa, Tomoyuki Ikuta, Yasunari Ding, Chenyang Miyaki, Shigeru Adachi, Nobuo Sci Rep Article Suppressing inflammation and abnormal subchondral bone turnover is essential for reducing osteoarthritis (OA) progression and pain relief. This study focused on calcitonin gene-related peptide (CGRP), which is involved in inflammation and bone metabolism, and investigated whether a CGRP receptor antagonist (rimegepant) could suppress OA progression and relieve pain in two OA models. C57BL/6 mice (10-week-old) underwent surgical destabilization of the medial meniscus, and Rimegepant (1.0 mg/kg/100 μL) or phosphate-buffered saline (100 μL) was administered weekly intraperitoneally after OA surgery and evaluated at 4, 8, and 12 weeks. In the senescence-accelerated mice (SAM)-prone 8 (SAMP8), rimegepant was administered weekly before and after subchondral bone sclerosis and sacrificed at 9 and 23 weeks, respectively. Behavioral assessment and immunohistochemical staining (CGRP) of the dorsal root ganglion (DRG) were conducted to assess pain. In DMM mice, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed in the rimegepant group. In SAMP8, synovitis, cartilage degeneration, and osteosclerosis were significantly suppressed by rimegepant at 9 weeks; however, not at 23 weeks. Behavioral assessment shows the traveled distance and the number of standings in the rimegepant group were significantly longer and higher. In addition, CGRP expression of the DRG was significantly lower in the rimegepant group at 8 and 12 weeks of DMM and 9 weeks of SAMP8 treatment. No adverse effects were observed in either of the mouse models. Inhibition of CGRP signaling has the potential to be a therapeutic target to prevent OA progression and suppress pain through the attenuation of subchondral bone sclerosis and synovitis. Nature Publishing Group UK 2023-09-16 /pmc/articles/PMC10505157/ /pubmed/37717108 http://dx.doi.org/10.1038/s41598-023-42673-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Nekomoto, Akinori Nakasa, Tomoyuki Ikuta, Yasunari Ding, Chenyang Miyaki, Shigeru Adachi, Nobuo Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis |
title | Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis |
title_full | Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis |
title_fullStr | Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis |
title_full_unstemmed | Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis |
title_short | Feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis |
title_sort | feasibility of administration of calcitonin gene-related peptide receptor antagonist on attenuation of pain and progression in osteoarthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10505157/ https://www.ncbi.nlm.nih.gov/pubmed/37717108 http://dx.doi.org/10.1038/s41598-023-42673-2 |
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