A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells
Abstract Purpose Mast cells are multifunctional in osteoarthritis (OA), and infiltration of activated mast cells likely contributes to disease severity and progression. However, the detailed mechanisms of action are unclear. The purpose of this study was to elucidate the role of mast cell infiltrati...
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doaj-0183d08af3e942559ea499ebe70541ef2021-09-12T11:29:01ZengSpringerOpenJournal of Experimental Orthopaedics2197-11532021-09-018111110.1186/s40634-021-00391-6A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cellsJunpei Dan0Masashi Izumi1Hiroko Habuchi2Osami Habuchi3Shogo Takaya4Yusuke Kasai5Ryuzo Hayashi6Koji Aso7Takahiro Ushida8Masahiko Ikeuchi9Department of Orthopedic Surgery, Kochi Medical School, Kochi UniversityDepartment of Orthopedic Surgery, Kochi Medical School, Kochi UniversityMultidisciplinary Pain Center, Aichi Medical UniversityMultidisciplinary Pain Center, Aichi Medical UniversityDepartment of Orthopedic Surgery, Kochi Medical School, Kochi UniversityDepartment of Orthopedic Surgery, Kochi Medical School, Kochi UniversityCenter for Innovative and Translational Medicine, Kochi UniversityDepartment of Orthopedic Surgery, Kochi Medical School, Kochi UniversityMultidisciplinary Pain Center, Aichi Medical UniversityDepartment of Orthopedic Surgery, Kochi Medical School, Kochi UniversityAbstract Purpose Mast cells are multifunctional in osteoarthritis (OA), and infiltration of activated mast cells likely contributes to disease severity and progression. However, the detailed mechanisms of action are unclear. The purpose of this study was to elucidate the role of mast cell infiltration in OA at histological level using a new mice model and to investigate pharmacological inhibitory effects of existing mast cell stabilizers in this model. Methods Mice were injected intra-articularly with monosodium iodoacetate (MIA 0.5 mg) or PBS on day 0, and PBS, with or without mast cells (MC: 1 × 106 cells) on day 14. They were divided into four groups: OA flare (MIA + MC), OA (MIA + PBS), MC non-OA (PBS + MC), and PBS non-OA (PBS + PBS). In OA flare, the MC stabilizer drug (tranilast: 400 mg/kg/day) or PBS was administered intraperitoneally from days 15 to 21. Results Histologically, modified Mankin score of the OA flare was significantly higher than that of OA (7.0 [1.8] vs. 3.3 [1.3], P < 0.05), and a larger number of mast cells was observed in OA flare than in OA (34.5 [6.3]/mm2 vs. 27.2 [2.3]/mm2, P < 0.05) on day 22. OA flare also showed acute exacerbation of pain and increased gene expression of pro-inflammatory cytokines and aggrecanase compared with OA. Administration of tranilast to OA flare-up provoked significant improvements in term of histological changes, pain, and gene expression at day 22. Conclusion Our novel model possibly mimics OA flare conditions, which may open a new strategy of disease-modifying treatment for OA, focused on controlling the multiple functions of mast cells.https://doi.org/10.1186/s40634-021-00391-6Mast cellOsteoarthritisPainInflammationFlare |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Junpei Dan Masashi Izumi Hiroko Habuchi Osami Habuchi Shogo Takaya Yusuke Kasai Ryuzo Hayashi Koji Aso Takahiro Ushida Masahiko Ikeuchi |
spellingShingle |
Junpei Dan Masashi Izumi Hiroko Habuchi Osami Habuchi Shogo Takaya Yusuke Kasai Ryuzo Hayashi Koji Aso Takahiro Ushida Masahiko Ikeuchi A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells Journal of Experimental Orthopaedics Mast cell Osteoarthritis Pain Inflammation Flare |
author_facet |
Junpei Dan Masashi Izumi Hiroko Habuchi Osami Habuchi Shogo Takaya Yusuke Kasai Ryuzo Hayashi Koji Aso Takahiro Ushida Masahiko Ikeuchi |
author_sort |
Junpei Dan |
title |
A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells |
title_short |
A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells |
title_full |
A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells |
title_fullStr |
A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells |
title_full_unstemmed |
A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells |
title_sort |
novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells |
publisher |
SpringerOpen |
series |
Journal of Experimental Orthopaedics |
issn |
2197-1153 |
publishDate |
2021-09-01 |
description |
Abstract Purpose Mast cells are multifunctional in osteoarthritis (OA), and infiltration of activated mast cells likely contributes to disease severity and progression. However, the detailed mechanisms of action are unclear. The purpose of this study was to elucidate the role of mast cell infiltration in OA at histological level using a new mice model and to investigate pharmacological inhibitory effects of existing mast cell stabilizers in this model. Methods Mice were injected intra-articularly with monosodium iodoacetate (MIA 0.5 mg) or PBS on day 0, and PBS, with or without mast cells (MC: 1 × 106 cells) on day 14. They were divided into four groups: OA flare (MIA + MC), OA (MIA + PBS), MC non-OA (PBS + MC), and PBS non-OA (PBS + PBS). In OA flare, the MC stabilizer drug (tranilast: 400 mg/kg/day) or PBS was administered intraperitoneally from days 15 to 21. Results Histologically, modified Mankin score of the OA flare was significantly higher than that of OA (7.0 [1.8] vs. 3.3 [1.3], P < 0.05), and a larger number of mast cells was observed in OA flare than in OA (34.5 [6.3]/mm2 vs. 27.2 [2.3]/mm2, P < 0.05) on day 22. OA flare also showed acute exacerbation of pain and increased gene expression of pro-inflammatory cytokines and aggrecanase compared with OA. Administration of tranilast to OA flare-up provoked significant improvements in term of histological changes, pain, and gene expression at day 22. Conclusion Our novel model possibly mimics OA flare conditions, which may open a new strategy of disease-modifying treatment for OA, focused on controlling the multiple functions of mast cells. |
topic |
Mast cell Osteoarthritis Pain Inflammation Flare |
url |
https://doi.org/10.1186/s40634-021-00391-6 |
work_keys_str_mv |
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