Baron Roland, Rawadi Georges
Yale University School of Medicine, New Haven, CT 06520-8044, USA.
Curr Osteoporos Rep. 2007 Jun;5(2):73-80. doi: 10.1007/s11914-007-0006-0.
Human genetic studies have firmly established a link between bone mass in humans and gain-of-function or loss-of-function mutations in a Wnt coreceptor, low-density lipoprotein receptor-related protein 5 (LRP5), or in the Wnt antagonist sclerostin, and several molecular genetic studies in mice have consistently confirmed the critical importance of the Wnt signaling pathway in skeletal biology and disease. In what may be a novel paradigm, the ubiquitous nature of LRP5/6 and Wnt signaling is counterbalanced by the bone-restricted and regulated expression of Wnt antagonists such as sclerostin and Dickkopf-1 (Dkk1) in adult tissues, offering new and potentially safe therapeutic means of intervention to stimulate bone formation.
人类遗传学研究已确凿地证实了人类骨量与Wnt共受体低密度脂蛋白受体相关蛋白5（LRP5）或Wnt拮抗剂硬化蛋白中的功能获得或功能丧失突变之间的联系，并且小鼠中的多项分子遗传学研究也一致证实了Wnt信号通路在骨骼生物学和疾病中的至关重要性。在一种可能是全新的模式中，LRP5/6和Wnt信号的普遍存在性被成年组织中诸如硬化蛋白和Dickkopf-1（Dkk1）等Wnt拮抗剂在骨骼中的限制性和调节性表达所平衡，这为刺激骨形成提供了新的且可能安全的治疗干预手段。
