Phorbol 12‑myristate 13‑acetate (PMA) suppresses high Ca2+‑enhanced adipogenesis in bone marrow stromal cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K01836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: Katoh Youichi 順天堂大学, 医学部, 教授 (00231259)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 骨髄脂肪変性 / 動脈硬化 / 再生血管 / カルシウムイオン / 骨髄間質細胞 / 間葉系幹細胞

Outline of Final Research Achievements

We have previously reported that increased extracellular and intracellular Ca2+ ([Ca2+]o & [Ca2+]i) lead to adipocyte accumulation in bone marrow stromal cells (BMSCs). In the present study, we examined the effects of the diacylglycerol analog phorbol 12-myristate 13-acetate (PMA) on proliferation and adipogenesis of mouse primary BMSCs. PMA suppressed the expression of both C/EBPα and PPARγ under normal adipogenesis, adipogenesis + CaCl2, and adipogenesis + ionomycin conditions. PMA enhanced proliferation under normal adipogenesis conditions but suppressed proliferation under adipogenesis + CaCl2 and adipogenesis + ionomycin conditions. PMA did not affect the accumulation of adipocytes under normal adipogenesis conditions but suppressed adipocyte accumulation under adipogenesis + CaCl2 and adipogenesis + ionomycin conditions. These results suggest that the PMA-dependent pathway is an important signaling pathway to suppress high Ca2+-enhanced adipocyte accumulation.

Free Research Field

動脈硬化、血管再生

Academic Significance and Societal Importance of the Research Achievements

骨髄脂肪化は特に高齢者の骨折や貧血の一因であり、治療標的として注目されている。本研究では、高濃度の細胞外カルシウム ([Ca2+]o)が特異的に骨髄脂肪化をもたらすメカニズムの同定を試みた。プロテインキナーゼC（PKC）を介したシグナル伝達経路が骨髄脂肪化に重要であることを突きとめ、PKC の活性化薬であるホルボールエステルPMAがCaイオンの骨髄脂肪化促進作用を抑制することを報告した (Hashimoto-R, Katoh-Y et al. J Physiol Sci 69: 741-748, 2019)。PKC の活性化薬が、高齢者の病的骨折減少への新たな治療戦略として期待される。