Wnt signaling and the regulation of bone mass

被引：29

作者：

Baron R. ^{[1
]}

Rawadi G. ^{[1
]}

机构：

[1] Yale University, School of Medicine, New Haven, CT 06520-8044

来源：

Current Osteoporosis Reports | 2007年 / 5卷 / 2期

关键词：

Bone Mineral Density; Bone Mass; Regulate Bone Formation; High Bone Mass Phenotype; Sclerostin Monoclonal Antibody;

D O I：

10.1007/s11914-007-0006-0

中图分类号：

学科分类号：

摘要：

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. Copyright © 2007 by Current Medicine Group LLC.

引用

页码：73 / 80

页数：7

共 62 条

[1]

Aubin J.E., Triffit J.T., Mesenchymal stem cells and osteoblast differentiation, Principles of Bone Biology, pp. 59-82, (2002)

[2]

Khosla S., Minireview: The OPG/RANKL/RANK system, Endocrinology, 142, pp. 5050-5055, (2001)

[3]

Suda T., Takahashi N., Udagawa N., Et al., Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families, Endocr Rev, 20, pp. 345-357, (1999)

[4]

Simonet W.S., Lacey D.L., Dunstan C.R., Et al., Osteoprotegerin: A novel secreted protein involved in the regulation of bone density, Cell, 89, pp. 309-319, (1997)

[5]

Deaton D.N., Tavares F.X., Design of cathepsin K inhibitors for osteoporosis, Curr Top Med Chem, 5, pp. 1639-1675, (2005)

[6]

Zaidi M., Troen B., Moonga B.S., Abe E., Cathepsin K, osteoclastic resorption, and osteoporosis therapy, J Bone Miner Res, 16, pp. 1747-1749, (2001)

[7]

Zhao C., Irie N., Takada Y., Et al., Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis, Cell Metab, 4, pp. 111-121, (2006)

[8]

Boyden L.M., Mao J., Belsky J., Et al., High bone density due to a mutation in LDL-receptor-related protein 5, N Engl J Med, 346, pp. 1513-1521, (2002)

[9]

Gong Y., Slee R.B., Fukai N., Et al., LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development, Cell, 107, pp. 513-523, (2001)

[10]

Little R.D., Carulli J.P., Del Mastro R.G., Et al., A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait, Am J Hum Genet, 70, pp. 11-19, (2002)

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