Role of M2 macrophages-produced neuropeptides in inflammatory-independent low back pain
| Project/Area Number |
20K09510
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内田 健太郎 北里大学, 医学部, 講師 (50547578)
大久保 直 北里大学, 医学部, 准教授 (10450719)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | マクロファージ / 腰痛 / 非炎症性 / M2 polarization / M2 マクロファージ / 線維輪 / M2極性化 / TGF-β / 非炎症下 / 椎間板 |
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| Outline of Research at the Start |
椎間板傷害モデル、KOマウスおよび臨床検体を駆使してM2マクロファージおよびM2マクロファージが産生する神経ペプチドを介した炎症非依存性の腰痛メカニズムを明らかにする。1. マウス腰椎椎間板傷害モデルにM2マクロファージ選択的除去剤を投与後、行動解析を行うことでM2マクロファージの腰痛への関与を明らかにする。2. M2マクロファージ産生神経ペプチドKOマウスを用いてM2マクロファージ由来神経ペプチドの腰痛への関与を検討する。3. 手術時に採取したヒト椎間板組織を用いたトランスレーショナルスタディを展開し、神経ペプチド、M2マクロファージマーカーの発現と腰痛の関連性を検討する。
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| Outline of Final Research Achievements |
Pathology of intervertebral discs (IVDs) is a major factor in chronic low back pain (LBP). A number of studies have reported that inflammatory condition plays a pivotal role in the pathology of IVD. However, the mechanism of pain mechanisms in non-inflammatory states remain unclear. We found that Peptide Lv expression increased in M2 macrophages. TGF-b stimulate M2 macrophages polarization and inhibition in TGF-b signaling reduced M2 macrophages in mice IVD injury model. In addition, we found that SEMA7A play an important role for M2 polarization. Our findings may provide novel therapeutic targets to treat LBP.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢社会を迎えた我が国において腰痛治療は極めて重要である。本研究は非炎症性メディエータによる腰痛という新たな病態の一端を明らかにしたものであり、高い社会的意義を有するものと考えられる。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs2022
Author(s)
Miyagi M, Uchida K, Inoue S, Takano S, Nakawaki M, Kawakubo A, Sekiguchi H, Nakazawa T, Imura T, Saito W, Shirasawa E, Kuroda A, Ikeda S, Yokozeki Y, Mimura Y, Akazawa T, Takaso M, Inoue G.
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Journal Title
Int J Mol Sci
Volume: 23
Issue: 6
Pages: 2973-2973
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of CD14-positive cells in inflammatory cytokine and pain-related molecule expression in human degenerated intervertebral discs2020
Author(s)
Miyagi M, Uchida K, Takano S, Nakawaki M, Sekiguchi H, Nakazawa T, Imura T, Saito W, Shirasawa E, Kawakubo A, Akazawa T, Inoue G, Takaso M
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Journal Title
J Orthop Res
Volume: -
Issue: 8
Pages: 1755-1762
DOI
Related Report
Peer Reviewed
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