Regulation of aging via regulating calcium homeostasis through a transmembrane protein Enpp1

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02930
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Keio University
• Principal Investigator: MIYAMOTO Takeshi 慶應義塾大学, 医学部(信濃町), 特任教授 (70383768)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 整形外科

Outline of Final Research Achievements

Osteoporosis is developed by various causes such as menopause and aging, and is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Mechanisms underlying bone loss owing to gonadal dysfunction such as menopause was recently clarified, however, those underlying aging dependent bone loss remained unclear. We utilized tip toe walk (ttw) mouse, which is a natural loss of function mutation mouse of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1), a transmembrane protein, and clarified that ttw mice exhibited significant bone loss under a feeding of high phosphate diet. We also found that ectopic ossification was seen in ttw mice fed a high phosphate diet. Thus, we concluded that Enpp1 was requited to regulate calcium homeostasis through regulating phosphate metabolism.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

近年の超高齢社会の到来により、骨粗鬆症患者数と骨粗鬆症に伴う脆弱性骨折数は増加の一途を辿っており、その対策は喫緊の課題である。本研究成果はカルシウム代謝の恒常性がリン代謝制御を介して制御されていることを明らかにした点、またその制御を膜貫通型分子であるectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1)が担っていることを解明した点で学術的に有意義であり、またリン代謝を通じてカルシウムの異所性沈着が制御されているという、骨粗鬆症の発症機構の新たな可能性を示し得た点で社会的にも意義がある研究であると考えている。