Research for the development of methods to control age-related diseases and bone diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K20496
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Multi-year Fund
• Review Section: Studies on the Super-Aging Society
• Research Institution: Juntendo University (2021-2022); The University of Tokyo (2020)
• Principal Investigator: Negishi Takako (古賀貴子) 順天堂大学, 大学院医学研究科, 特任准教授 (90451905)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 骨代謝学 / 加齢性疾患 / 骨粗鬆症 / 破骨細胞 / 骨芽細胞

Outline of Final Research Achievements

Using a mouse model of Alzheimer’s disease, we found that amyloid-b deposited in bone tissue and caused bone loss, suggesting that deposition of amyloid-b in bone tissue may occur independently of its deposition in the brain and of impaired cognitive function and learning. In this mouse model, mild exercise by treadmill induced tibia fracture susceptibility resulted from gene expression changes in certain circulating cells and knee joint cells around the time of onset of behavioral abnormalities. It was suggested that a degeneration-dependent humoral factor in the brain causes bone fragility. This bone fragility was not detected in mice with spontaneous memory deficits, suggesting neuropathic amyloid-b-dependent bone fragility.

Free Research Field

骨代謝学

Academic Significance and Societal Importance of the Research Achievements

加齢とともに心身の活力（運動機能や認知機能等）が低下するフレイルやロコモーティブシンドローム（ロコモ）は要介護状態の前段階であり、フレイルや初期のロコモの段階で積極的に改善をめざすことができれば超高齢社会で要介護人口の増加に歯止めをかける一助となる。その意味で、リハビリや運動療法は初期の認知症やフレイルを発症した高齢者に推奨される。リハビリや運動療法が認知症にも効果があることを分子レベルで証明できれば、それを人為的な治療・薬剤開発の基盤にできる。運動器と脳・神経系の関連を担う因子を探求することは、学術的にも新たな発見につながり、社会的にも新規制御法の開発に繋がる。