Activation of the cGAS-STING pathway in bone remodeling microenvironment aging cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K21004
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Hyogo Medical University
• Principal Investigator: Hattori Hirokazu 兵庫医科大学, 医学部, 助教 (50836103)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 破骨前駆細胞 / 老化 / 骨微小環境

Outline of Final Research Achievements

RAW264.7 cells, which are macrophage-like osteoclast precursor cells, showed decreased osteoclast differentiation with senescence, activating the cGAS-STING pathway and inducing SASP. When senescent RAW264.7 cells were treated with STING inhibitor, the induction of SASP was suppressed along with the inhibition of cGAS-STING pathway, and osteoclast differentiation was restored. The STING pathway or suppressed SASP factors were suggested to be associated with factors that regulate osteoclast differentiation.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

破骨前駆細胞は老化するとcGAS-STING経路が活性化し、SASPが誘導され、また、STING阻害剤の使用により、SASPを抑制でき、破骨細胞分化能が回復する可能性が示唆された。c-GAS-STING経路と破骨細胞分化能に関連があることが考えられ、骨粗鬆症を代表とした加齢性の骨代謝性疾患のさらなる病態解明や、新規治療薬の開発につながるのではないかと考えている。