The Anti-Osteoanabolic Function of Sclerostin is Blunted in Mice Carrying a High Bone Mass Mutation of Lrp5

Journal of Bone and Mineral Research

Volumn 30, Issue 7, 2015, Pages 1175-1183

  Yorgan, Timur A ^a   Peters, Stephanie ^a   Jeschke, Anke ^a   Benisch, Peggy ^b   Jakob, Franz ^b   Amling, Michael ^a   Schinke, Thorsten ^a  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

BONE FORMATION; KRM2; LRP5; SCLEROSTIN; WNT SIGNALING

Indexed keywords

LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; MEMBRANE PROTEIN; OSTEOGENIC PROTEIN 1; SCLEROSTIN; ANABOLIC AGENT; COLLAGEN TYPE 1; GLYCOPROTEIN; SOST PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIOSTEOANABOLIC ACTIVITY; ARTICLE; BIOLOGICAL ACTIVITY; BONE MASS; BONE MINERALIZATION; BONE REMODELING; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED STUDY; ENZYME MECHANISM; FEMALE; GENE EXPRESSION; GENE INTERACTION; GENE MUTATION; GENE OVEREXPRESSION; IN VIVO STUDY; MORPHOMETRICS; MOUSE; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOCLASTOGENESIS; OSTEOLYSIS; OSTEOSCLEROSIS; OSTEOSYNTHESIS; PHENOTYPIC VARIATION; PHYSIOLOGICAL PROCESS; PROMOTER REGION; TRANSGENE; WNT SIGNALING PATHWAY; ALLELE; ANIMAL; BONE; CELL CULTURE; GENETICS; METABOLISM; MICRO-COMPUTED TOMOGRAPHY; MUTATION; ORGAN SIZE; PATHOLOGY; PHENOTYPE; RADIOGRAPHY;

ALLELES; ANABOLIC AGENTS; ANIMALS; BONE AND BONES; BONE REMODELING; CELLS, CULTURED; COLLAGEN TYPE I; GLYCOPROTEINS; LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-5; MICE; MUTATION; ORGAN SIZE; OSTEOBLASTS; PHENOTYPE; TRANSGENES; X-RAY MICROTOMOGRAPHY;

EID: 84931956359     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2461     Document Type: Article

References (52)

1. Saito-Diaz K, Chen TW, Wang X, et al., The way Wnt works: components and mechanism. Growth Factors. 2013; 31 (1): 1-31.
2. Baron R, Kneissel M., WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013; 19 (2): 179-92.
3. Clevers H, Nusse R., Wnt/beta-catenin signaling and disease. Cell. 2012; 149 (6): 1192-205.
4. Tamai K, Semenov M, Kato Y, et al., LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000; 407 (6803): 530-5.
5. Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC,. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature. 2000; 407 (6803): 535-8.
6. Boyden LM, Mao J, Belsky J, et al., High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002; 346 (20): 1513-21.
7. Gong Y, Slee RB, Fukai N, et al., LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001; 107 (4): 513-23.
8. Little RD, Carulli JP, Del Mastro RG, 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 (1): 11-9.
9. Kato M, Patel MS, Levasseur R, 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 (2): 303-14.
10. Babij P, Zhao W, Small C, et al., High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res. 2003; 18 (6): 960-74.
11. Cui Y, Niziolek PJ, MacDonald BT, et al., Lrp5 functions in bone to regulate bone mass. Nat Med. 2011; 17 (6): 684-91.
12. Glass DA II, Bialek P, Ahn JD, et al., Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell. 2005; 8 (5): 751-64.
13. Holmen SL, Zylstra CR, Mukherjee A, et al., Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem. 2005; 280 (22): 21162-8.
14. Kramer I, Halleux C, Keller H, et al., Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol. 2010; 30 (12): 3071-85.
15. Ai M, Holmen SL, Van Hul W, Williams BO, Warman ML,. Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling. Mol Cell Biol. 2005; 25 (12): 4946-55.
16. Morvan F, Boulukos K, Clement-Lacroix P, 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 (6): 934-45.
17. Li J, Sarosi I, Cattley RC, et al., Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone. 2006; 39 (4): 754-66.
18. Mao B, Wu W, Davidson G, et al., Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature. 2002; 417 (6889): 664-7.
19. Schulze J, Seitz S, Saito H, et al., Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2. PLoS One. 2010; 5 (4): e10309.
20. Weivoda MM, Oursler MJ,. Developments in sclerostin biology: regulation of gene expression, mechanisms of action, and physiological functions. Curr Osteoporos Rep. 2014; 12 (1): 107-14.
21. Lewiecki EM,. Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases. Ther Adv Musculoskelet Dis. 2014; 6 (2): 48-57.
22. Balemans W, Ebeling M, Patel N, et al., Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001; 10 (5): 537-43.
23. Balemans W, Patel N, Ebeling M, et al., Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet. 2002; 39 (2): 91-7.
24. Nolan K, Thompson TB,. The DAN family: modulators of TGF-β signaling and beyond. Protein Sci. 2014 Aug; 23 (8): 999-1012.
25. Li X, Zhang Y, Kang H, et al., Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005; 280 (20): 19883-7.
26. Semenov M, Tamai K, He X., SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005; 280 (29): 26770-5.
27. Ellies DL, Viviano B, McCarthy J, et al., Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res. 2006; 21 (11): 1738-49.
28. Semenov MV, He X., LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem. 2006; 281 (50): 38276-84.
29. Balemans W, Piters E, Cleiren E, et al., The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008; 82 (6): 445-53.
30. Kedlaya R, Veera S, Horan DJ, et al., Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome. Sci Transl Med. 2013; 5 (211): 211ra158.
31. Chang MK, Kramer I, Keller H, et al., Reversing LRP5-dependent osteoporosis and SOST deficiency-induced sclerosing bone disorders by altering WNT signaling activity. J Bone Miner Res. 2014; 29 (1): 29-42.
32. Choi HY, Dieckmann M, Herz J, Niemeier A., Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo. PLoS One. 2009; 4 (11): e7930.
33. Leupin O, Piters E, Halleux C, et al., Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem. 2011; 286 (22): 19489-500.
34. Winkler DG, Sutherland MK, Geoghegan JC, et al., Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003; 22 (23): 6267-76.
35. Kusu N, Laurikkala J, Imanishi M, et al., Sclerostin is a novel secreted osteoclast-derived bone morphogenetic protein antagonist with unique ligand specificity. J Biol Chem. 2003; 278 (26): 24113-7.
36. Niziolek PJ, Farmer TL, Cui Y, Turner CH, Warman ML, Robling AG,. High-bone-mass-producing mutations in the Wnt signaling pathway result in distinct skeletal phenotypes. Bone. 2011; 49 (5): 1010-9.
37. Niziolek PJ, Warman ML, Robling AG,. Mechanotransduction in bone tissue: The A214V and G171V mutations in Lrp5 enhance load-induced osteogenesis in a surface-selective manner. Bone. 2012; 51 (3): 459-65.
38. Rossert J, Eberspaecher H, de Crombrugghe B., Separate cis-acting DNA elements of the mouse pro-alpha 1(I) collagen promoter direct expression of reporter genes to different type I collagen-producing cells in transgenic mice. J Cell Biol. 1995; 129 (5): 1421-32.
39. Albers J, Keller J, Baranowsky A, et al., Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin. J Cell Biol. 2013; 200 (4): 537-49.
40. Parfitt AM, Drezner MK, Glorieux FH, et al., Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987; 2 (6): 595-610.
41. Schulze J, Bickert T, Beil FT, et al., Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells. J Bone Miner Res. 2011; 26 (4): 704-17.
42. Doube M, Klosowski MM, Arganda-Carreras I, et al., BoneJ: free and extensible bone image analysis in ImageJ. Bone. 2010; 47 (6): 1076-9.
43. Schindelin J, Arganda-Carreras I, Frise E, et al., Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9 (7): 676-82.
44. Dacquin R, Starbuck M, Schinke T, Karsenty G., Mouse alpha1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast. Dev Dyn. 2002; 224 (2): 245-51.
45. Li X, Ominsky MS, Niu QT, et al., Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res. 2008; 23 (6): 860-9.
46. Rhee Y, Allen MR, Condon K, et al., PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling. J Bone Miner Res. 2011; 26 (5): 1035-46.
47. Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F., Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol. 2002; 22 (4): 1172-83.
48. Jukkola T, Sinjushina N, Partanen J., Drapc1 expression during mouse embryonic development. Gene Expr Patterns. 2004; 4 (6): 755-62.
49. Yadav VK, Ryu JH, Suda N, et al., Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008; 135 (5): 825-37.
50. Kode A, Obri A, Paone R, Kousteni S, Ducy P, Karsenty G., Lrp5 regulation of bone mass and serotonin synthesis in the gut. Nat Med. 2014; 20 (11): 1228-9.
51. Cui Y, Niziolek PJ, MacDonald BT, et al., Reply to Lrp5 regulation of bone mass and gut serotonin synthesis. Nat Med. 2014; 20 (11): 1229-30.
52. McClung MR, Grauer A, Boonen S, et al., Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014; 370 (5): 412-20.