Assessment for the regulatory mechanism of osteocyte network on bone mineralization

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16928
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Hokkaido University
• Principal Investigator: Hongo Hiromi 北海道大学, 歯学研究院, 助教 (00778970)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 骨基質石灰化 / 骨細胞 / 基質小胞性石灰化

Outline of Final Research Achievements

We analyzed the regulation of bone matrix calcification by osteocytic networks in hyperphosphatemic/hypercalcemic kl/kl mice and diabetic model SDT fatty rats. Osteocytes of kl/kl mice showed positivity of DMP-1 and osteopontin, a SIBLING family protein with a calcification inhibitory function, osteocytes from SDT fatty rats revealed immunoreactivity of not only DMP-1 but also osteocalcin and showed unmineralized bone matrix in both groups. Thus it suggested that osteocytes were involved in the calcification of bone matrix, since the disruption of the osteocytic lacunae-canalicular system due to pathological conditions results in abnormal calcification maintenance and mineral balance regulation in the bone matrix.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

これまでに骨細胞が基質小胞性石灰化を積極的に調整してゆくという概念について明確に述べた論文や研究はなく、本研究は骨細胞ネットワークがDMP-1やosteocalcinなどのリン酸カルシウム結晶結合蛋白の分泌制御を中心に、基質小胞性石灰化に関与する可能性を強く示唆している。また、石灰化異常に関する病態はくる病・骨軟化症だけでなく、低ホスファターゼ症や腎疾患などに付随する異所性石灰化・心血管イベントなど多岐にわたって認められる現象であり、これらの病態を解明・改善する一助となる研究といえる。