Phosphate sensing and expression mechanism of genes responsible for hypophosphatemic rickets in osteocytes: Involvement of Pit1

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09635
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• 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), 環境影響部門, 研究員(移行) (50455549)
• Co-Investigator(Renkei-kenkyūsha): MICHIGAMI Toshimi 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)・環境影響部門, 部長 (00301804)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: リン / Pit-1

Outline of Final Research Achievements

As osteoblasts mature, they acquire the expression of multiple molecules involved in phosphate (Pi) metabolism. Osteoblasts/osteocytes may sense and respond to alterations in Pi availability in their microenvironment. However, the involvement of type III sodium/phosphate co-transporters, Pit-1 and Pit-2, in Pi handling in osteoblasts/osteocytes is unclear. In the current study, we have investigated the role of Pit-1 and Pit-2 in the responsiveness of osteoblasts to Pi by deleting Pit-1 and Pit-2 from MC3T3-E1 cells using CRISPR/Cas9 systems. Deletion of Pit-1 in osteoblastic cells affected the response to increased extracellular Pi. Although Pit-2 may play a role to mediate a long-term effect of high Pi in osteoblastic cells, it appears to be dispensable for responding to acute Pi elevation. In conclusion, Pit-1 and Pit-2 might have different roles in osteoblasts.

Free Research Field

骨ミネラル代謝学