Elucidating the mechanisms of bone metabolism disorders caused by abnormal estrogen secretion in young female athletes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16688
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Ehime University
• Principal Investigator: Ikedo Aoi 愛媛大学, プロテオサイエンスセンター, 特定研究員 (60834520)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: エストロゲン / CAR細胞 / 骨折治癒

Outline of Final Research Achievements

We focused on Cxcl12 abundant reticular cells (CAR cells), which are bone marrow mesenchymal stem cells with a high contribution to fracture repair and high expression of estrogen receptor alpha (ERα), and the aim of this study was to clarify estrogen effects on the regulation of fracture healing by CAR cells.
First, CAR cell-specific ERα-deficient mice (cKO) were generated and observed during the fracture healing process. However, no group differences were found in the callus volume at 10 and 14 days after fracture. On the other hand, bone mineral density was significantly lower and bone marrow fat volume was significantly increased in cKO compared with CON in intact tibias and femurs collected at 23 weeks of age. We will perform studies of this phenotype in detail in the future.

Free Research Field

スポーツ健康科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、CAR細胞特異的にERα欠損させた時の骨折治癒への影響を検出することができなかった。しかし、骨折治癒に関わる間葉系幹細胞は、骨膜や成長板にも存在するため、これらの細胞がCAR細胞におけるERα欠損の影響をマスクしている可能性も考えられた。一方で、cKOマウスの無処置の脛骨および大腿骨において、骨密度の低下及び骨髄脂肪の増加が見られたことは、閉経後骨粗鬆に見られる骨髄脂肪の増加の機序を明らかにし、治療標的を発見できる可能性がある。従って、今後はこの表原型について詳細な検証を行い、治療法の開発を目指す。