Molecular mechanism of calcinosis in systemic sclerosis
| Project/Area Number |
19K08921
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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 54020:Connective tissue disease and allergy-related
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 強皮症 / 石灰沈着症 / 骨芽細胞 |
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| Outline of Research at the Start |
SScの軟部組織中で沈着している成分がハイドロキシアパタイトであるかといった基本についてリン酸カルシウムの染色で検証する。また、その産生細胞である骨芽細胞が患者病変部に実際に存在するかについて、免疫染色と網羅的遺伝子発現で骨芽細胞マーカーの解析を行う。次に、骨芽細胞は軟部組織には本来存在しないため、間葉系細胞からの分化および細胞動員が想定される。この細胞源が循環血液中細胞や局所（関節・腱鞘滑膜）など、どこから供給されるかをSSc患者の末梢血検体および、マウス由来の関節・腱組織を用いて検証する。
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| Outline of Final Research Achievements |
We investigated the mechanism of subcutaneous calcification seen in scleroderma patients. First, it was confirmed by staining that the calcified component was hydroxyapatite. In pathology, mononuclear cells gathered around the deposited lesion and the osteoblast marker ALP was positive. When the calcified tissue was cultured, CD90 and osteocalcin-positive cells proliferated. The tissue also continued to increase spontaneously, and ALP-positive cells were scattered in it. Therefore, a mechanism was assumed in which the mesenchymal cells in the tissue differentiated into osteoblasts and ectopically produced the calcification component. Therefore, it was shown that when a well-used therapeutic agent was added to a culture system that differentiates mesenchymal stem cells into osteoblasts, calcification deposition and extracellular matrix-related gene expression were suppressed.
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| Academic Significance and Societal Importance of the Research Achievements |
強皮症の皮下石灰沈着症は、組織中の間葉系の細胞が骨芽細胞に分化して異所性に石灰成分を産生し、病態を形成する機序であることが示唆された。これは、血管石灰化など他の異所性石灰沈着症と共通した分子機序を有し、本研究の成果は間葉系幹細胞分野の進歩の一助になりうる。また、既存の薬物治療の効果は乏しく、アンメットニーズとなっている。本研究で分子標的を明らかにすることで、有効性の高い治療薬の開発が期待できる。
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Report
(4 results)
Research Products
(9 results)
