Wntシグナル経路の遺伝子異常による骨量増加

Wnt signal and Bone. Genetic impairments of Wnt signaling pathways in hereditary high bone mass syndrome and sclerostosis diseases.

　骨量増加や骨硬化を呈する遺伝性疾患の解析から，骨芽細胞や骨細胞におけるWntシグナルの活性化が，成長後の骨形成の促進において最も重要かつ生理的な役割を果たすことが明らかになった。とりわけ，Wntとそのシグナル伝達受容体であるFrizzledの結合を媒介するLRP5，およびWntの受容体への結合を阻害するsclerostinは骨特異性が高い分子であり，その生理的な役割と共に骨粗鬆症の治療標的としての重要性が注目されている。

　Investigations of hereditary skeletal diseases, such as high bone mass syndrome and sclerostosis diseases, have opened the door to understand molecular mechanisms for bone formation. Signal transduction activated by Wnt-Frizzled has been established to be critically and physiologically involved in the stimulation of bone formation by osteoblasts. LRP5, a co-receptor that binds Wnt to activate signal transduction through Frizzled, and sclerostin, an inhibitor of Wnt, are both indispensable molecules that stimulate and inhibit bone formation, respectively in health and diseases. Those are emerging target molecules to develop novel therapeutic drugs for osteoporosis.