Molecular mechanism of calcinosis in systemic sclerosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08921
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Nippon Medical School
• Principal Investigator: Shirai Yuichiro 日本医科大学, 医学部, 講師 (70528801)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 強皮症 / 石灰沈着症 / 骨芽細胞

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.

Free Research Field

強皮症

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。