SFRP5 regulates bone metabolisms independent of WNT signaling

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Okayama University of Science
• Principal Investigator: Murakami Kohei 岡山理科大学, 獣医学部, 講師 (60791837)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: WNTシグナル / 骨代謝 / 骨芽細胞 / 破骨細胞

Outline of Final Research Achievements

I identified 120 proteins that interact with Sfrp5. We performed knockdown of seven of these proteins, but found no effect of counteracting the action of Sfrp5, and could not identify factors that interact with Sfrp5 in its effect on osteoblasts.
Using CAGE-seq, we identified Egr1 as a transcription factor activated by Sfrp5. When Egr1 was knocked down, the action of Sfrp5 disappeared, suggesting that Sfrp5 activates Egr1 and promotes osteoblast differentiation.
To confirm the effect in vivo, we administered an adeno-associated virus that overexpresses Sfrp5 to mice. Although osteoclast formation was suppressed, no increase in bone mass was observed.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

本課題はWNTアンタゴニストとして知られているSFRP5が、WNT非依存的に骨芽細胞に作用するという仮説に基づいて実験を行った。その結果、転写因子Egr1を活性化することで骨芽細胞に作用していることがわかった。Egr1はERK経路などのMAPKシグナル伝達経路の下流に位置する。今後、SFRP5がどのようにEgr1を活性化するのかを解明できれば、骨代謝や発生において中心的な役割を果たすWNTシグナルの新たな一面を明らかにし、様々な分野への応用が期待できる。