Role of type III sodium/phosphate co-transporters in osteoblast differentiation and mineralization

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07866
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Osama Woman's and Children's Hospital
• Principal Investigator: Yamazaki Miwa (若林美和) 地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 骨発育疾患研究部門(旧環境影響部門), 流動研究員 (50455549)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: リン / Pit1 / Pit2

Outline of Final Research Achievements

In skeletons, extracellular phosphate (Pi) exerts various actions. Although these multiple actions of extracellular Pi on the skeletal cells are likely to be partly mediated by type III sodium/phosphate co-transporters Pit1 and Pit2, the details still remain unclear. In the current study, we generated osteoblastic cells lacking Pit1 or Pit2 by applying CRISPR/Cas9 genome editing. Our results demonstrated that ablation of Pit1 or Pit2 in the osteoblastic cell line led to accelerated mineralization, suppressed tissue-nonspecific alkaline phosphatase and altered the levels of extracellular and intracellular pyrophosphate and adenosine triphosphate, and we speculate that these changes might be partly mediated by changes in the availability of extracellular Pi.

Free Research Field

骨ミネラル代謝学

Academic Significance and Societal Importance of the Research Achievements

近年、血管や脳などの異所性の石灰化におけるPit1やPit2の関与が報告され、注目を浴びている。しかしながら、小児の成長に関わる骨芽細胞の分化や石灰化におけるPit1およびPit2の生理的な機能については充分な検討がなされておらず、本研究の学術的意義は大きい。