Wnt signaling in bone

Clinical Pediatric Endocrinology

Volumn 19, Issue 3, 2010, Pages 49-56

  Kubota, Takuo ^a,b   Michigami, Toshimi ^b   Ozono, Keiichi ^a  

^a OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b RESEARCH INSTITUTE FOR MATERNAL AND CHILD HEALTH   (Japan)

Author keywords

Bone metabolism; LRP5; LRP6; Sclerostin; Wnt signaling

Indexed keywords

BETA CATENIN; DICKKOPF 1 PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 6; PARATHYROID HORMONE RECEPTOR; SCLEROSTIN; WNT PROTEIN; WNT10B PROTEIN; WNT7B PROTEIN;

ADIPOGENESIS; BONE DENSITY; BONE MASS; BONE METABOLISM; CELL PROLIFERATION; DNA POLYMORPHISM; EMBRYO DEVELOPMENT; GENE EXPRESSION; GENE MUTATION; GENE TARGETING; HUMAN; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOLYSIS; PHENOTYPE; POINT MUTATION; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION;

EID: 77957105615     PISSN: 09185739     EISSN: 13477358     Source Type: Journal    
DOI: 10.1297/cpe.19.49     Document Type: Review

References (47)

1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001;285:785-95.
2. Liu YJ, Shen H, Xiao P, Xiong DH, Li LH, Recker RR, et al. Molecular genetic studies of gene identification for osteoporosis: a 2004 update. J Bone Miner Res 2006;21: 1511-35.
3. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001;107:513-23.
4. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 2002;346:1513-21.
5. Little RD, Carulli JR, Del Mastro RG, Dupuis J, Osborne M, Folz C, 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 2002;70:11-9.
6. Mani A, Radhakrishnan J, Wang H, Mani A, Mani M-A, Nelson-Williams C, et al. LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 2007;315:1278-82.
7. Khosla S, Westendorf JJ, Oursler MJ. Building bone to reverse osteoporosis and repair fractures. J Clin Invest 2008;118:421-8.
8. Williams BO, Insogna KL. Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone. J Bone Miner Res 2009;24:171-8.
9. Kubota T, Michigami T, Ozono K. Wnt signaling in bone metabolism. J Bone Miner Metab 2009;27:265-71.
10. Warden SJ, Robling AG, Haney EM, Turner CH, Bliziotes MM. The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). Bone 2009;46:4-12.
11. MacDonald BT, Tamai K, He X. Wnt/β-Catenin signaling: components, mechanisms, and diseases. Dev Cell 2009;17:9-26.
12. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004;20:781-810.
13. Balemans W, Van Hul W. The genetics of low-density lipoprotein receptor-related protein 5 in bone: a story of extremes. Endocrinology 2007;148:2622-9.
14. Ezura Y, Nakajima T, Urano T, Sudo Y, Kajita M, Yoshida H, et al. Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women. Bone 2007;40:997-1005.
15. Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 2008;371:1505-12.
16. van Meurs JB, Trikalinos TA, Ralston SH, Balcells S, Brandi ML, Brixen K, et al. GENOMOS Study. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA 2008;299:1277-90.
17. Kato M, Patel MS, Levasseur R, Lobov I, Chang BHJ, Glass 2nd DA, et al. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 2002;157:303-14.
18. Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 2008;135:825-37.
19. Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 2000;407:535-8.
20. Holmen SL, Giambernardi TA, Zylstra CR, Buckner-Berghuis BD, Resau JH, Hess JF, et al. Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res 2004;19:2033-40.
21. Kokubu C, Heinzmann U, Kokubu T, Sakai N, Kubota T, Kawai M, et al. Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis. Development 2004;131:5469-80.
22. Kubota T, Michigami T, Sakaguchi N, Kokubu C, Suzuki A, Namba N, et al. Lrp6 Hypomorphic Mutation Affects Bone Mass through Bone Resorption in Mice and Impairs Interaction with Mesd. J Bone Miner Res 2008;23:1661-71.
23. Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, et al. Inhibition of adipogenesis by Wnt signaling. Science 2000;289:950-3.
24. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 2005;132:49-60.
25. Tu X, Joeng KS, Nakayama KI, Nakayama K, Rajagopal J, Carroll TJ, et al. Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation. Dev Cell 2007;12:113-27.
26. Bennett CN, Ouyang H, Ma YL, Zeng Q, Gerin I, Sousa KM, et al. Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation. J Bone Miner Res 2007;22:1924-32.
27. Day TF, Guo X, Garrett-Beal L, Yang Y. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 2005;8:739-50.
28. Hill TP, Später D, Taketo MM, Birchmeier W, Hartmann C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 2005;8:727-38.
29. Glass 2nd DA, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, et al. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 2005;8:751-64.
30. Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere M-C, Bouxsein ML, et al. Essential Role of b-catenin in postnatal bone acquisition. J Biol Chem 2005;280:21162-8.
31. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 2005;280:19883-7.
32. Semënov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 2005;280:26770-5.
33. Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001;10:537-43.
34. Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 2001;68:577-89.
35. Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 2002;39:91-7.
36. Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D'Agostin D, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 2008;23:860-9.
37. Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 2005;19:1842-4.
38. Padhi D, Stouch B, Jang G, Fang L, Darling M, Glise H, et al. Anti-sclerostin antibody increases markers of bone formation in healthy postmenopausal women. J Bone Miner Res 2007;22:S37.
39. Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 2009;24:578-88.
40. Jilka RL. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 2007;40:1434-46.
41. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O'Brien CA, et al. Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 2005;146:4577-83.
42. Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone 2005;37:148-58.
43. O'Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, et al. Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLoS ONE 2008;3:e2942.
44. Morvan F, Boulukos K, Clément-Lacroix P, Roman Roman S, Suc-Royer I, Vayssière B, et al. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 2006;21:934-45.
45. Li J, Sarosi I, Cattley RC, Pretorius J, Asuncion F, Grisanti M, et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 2006;39:754-66.
46. Li X, Liu P, Liu W, Maye P, Zhang J, Zhang Y, et al. Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet 2005;37:945-52.
47. Bodine PV, Zhao W, Kharode YP, Bex FJ, Lambert AJ, Goad MB, et al. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol Endocrinol 2004;18:1222-37.