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2018 Fiscal Year Final Research Report

Elucidation of the osteoclast-derived cytokine-Wnt signaling network responsible for coupling between bone resorption and formation.

Research Project

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Project/Area Number 16H05144
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionMatsumoto Dental University

Principal Investigator

Takahashi Naoyuki  松本歯科大学, 総合歯科医学研究所, 特任教授 (90119222)

Co-Investigator(Kenkyū-buntansha) 宇田川 信之  松本歯科大学, 歯学部, 教授 (70245801)
小林 泰浩  松本歯科大学, 総合歯科医学研究所, 教授 (20264252)
中村 浩彰  松本歯科大学, 歯学部, 教授 (50227930)
南 康博  神戸大学, 医学研究科, 教授 (70229772)
荒 敏昭  松本歯科大学, 歯学部, 講師 (90387423)
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords破骨細胞 / 骨芽細胞 / カップリング因子 / クラストカイン / スクレロスチン / LIF / HtrA1
Outline of Final Research Achievements

Clastokines secreted by osteoclasts were analyzed. (1) Osteoclasts secreted LIF, which suppressed the secretion of sclerostin by osteocytes. Thus, osteoclasts promoted osteoblastic bone formation through the up-regulation of Wnt-βcatenin signals. (2) W9 peptides suppressed bone resorption activity of osteoclasts and suppressed sclerostin expression by osteocytes. Thus, W9 increased the alveolar bone mass. (3) Osteoclasts abundantly secreted Wnt5a. Wnt5a binds to its receptor, Ror2, which is expressed by osteoclasts. The Wnt5a-Ror2 signal in osteoclasts induced bone-resorbing activity through Daam2→ Rho→ PKN3→ cSrc/Pyk2 signals. (4) Osteoclasts specifically secreted HtrA1, which degraded OPG, suggesting that osteoclasts potentially prepare a microenvironment that is suitable for osteoclastogenesis. Thus, osteoclasts secrete various Clastokines that are involved in bone metabolism.

Free Research Field

生化学、骨代謝学

Academic Significance and Societal Importance of the Research Achievements

従来破骨細胞は骨吸収のみを行う細胞であると考えられてきた。しかし本研究より、破骨細胞は様々なクラストカインを分泌し、骨代謝とりわけ骨代謝共役を担っていることが示された。本研究成果は、破骨細胞がサイトカイン分泌細胞であるあるいは内分泌細胞であるという新しい考え方を示すことができたと考える。さらにLIFの作用を抑制する薬剤、W9ペプチド、HtrA1の阻害剤は特粗鬆症など代謝性骨疾患の治療薬となり得る可能性が示された。

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Published: 2020-03-30  

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