LRP5

Summary

Gene Symbol: LRP5
Description: LDL receptor related protein 5
Alias: BMND1, EVR1, EVR4, HBM, LR3, LRP-5, LRP7, OPPG, OPS, OPTA1, PCLD4, VBCH2, low-density lipoprotein receptor-related protein 5, low density lipoprotein receptor-related protein 5, low density lipoprotein receptor-related protein 7
Species: human
Products:     LRP5

Top Publications

  1. Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, et al. A mechanism for Wnt coreceptor activation. Mol Cell. 2004;13:149-56 pubmed
    LDL receptor related proteins 5 and 6 (LRP5/6) and their Drosophila homolog Arrow are single-span transmembrane proteins essential for Wnt/beta-catenin signaling, likely via acting as Wnt coreceptors...
  2. Hoang B, Kubo T, Healey J, Sowers R, Mazza B, Yang R, et al. Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. Int J Cancer. 2004;109:106-11 pubmed
    The Wingless-type (Wnt) family of proteins and its coreceptor LRP5 have recently been implicated in human skeletal development...
  3. Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280:26770-5 pubmed
    ..similarities with "high bone mass" diseases caused by "gain-of-function" mutations in the LRP5 gene, which encodes a coreceptor for Wnt signaling proteins...
  4. Semenov M, He X. LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem. 2006;281:38276-84 pubmed
    The low density lipoprotein (LDL) receptor-related protein 5 (LRP5) is a co-receptor for Wnt proteins and a major regulator in bone homeostasis...
  5. Kruk M, Ralston S, Albagha O. LRP5 Polymorphisms and response to risedronate treatment in osteoporotic men. Calcif Tissue Int. 2009;84:171-9 pubmed publisher
    ..Previous studies have shown that polymorphisms of the LRP5 gene are associated with bone mineral density (BMD), but the relationship between LRP5 polymorphisms and response ..
  6. Yu J, Ke Y, He J, Zhang H, Hu W, Hu Y, et al. No association between LRP5 gene polymorphisms and bone and obesity phenotypes in Chinese male-offspring nuclear families. Acta Pharmacol Sin. 2010;31:1464-9 pubmed publisher
    To investigate the effect of low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms on bone and obesity phenotypes in young Chinese men...
  7. He X, Semenov M, Tamai K, Zeng X. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development. 2004;131:1663-77 pubmed
    ..Low-density-lipoprotein receptor-related proteins 5 and 6 (Lrp5 and Lrp6) in vertebrates, and their Drosophila ortholog Arrow, are single-span transmembrane proteins that are ..
  8. Agueda L, Velázquez Cruz R, Urreizti R, Yoskovitz G, Sarrión P, Jurado S, et al. Functional relevance of the BMD-associated polymorphism rs312009: novel involvement of RUNX2 in LRP5 transcriptional regulation. J Bone Miner Res. 2011;26:1133-44 pubmed publisher
    b>LRP5 is an osteoporosis susceptibility gene. Association analyses reveal that individual single-nucleotide polymorphisms (SNPs) determine variation in bone mineral density (BMD) among individuals as well as fracture risk...
  9. Hartikka H, Makitie O, Männikkö M, Doria A, Daneman A, Cole W, et al. Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children. J Bone Miner Res. 2005;20:783-9 pubmed
    Three of 20 patients with juvenile osteoporosis were found to have a heterozygous mutation in the LRP5 gene. No mutations were found in the type I collagen genes...

More Information

Publications90

  1. Papathanasiou I, Malizos K, Tsezou A. Low-density lipoprotein receptor-related protein 5 (LRP5) expression in human osteoarthritic chondrocytes. J Orthop Res. 2010;28:348-53 pubmed publisher
    ..the Wnt/beta-catenin pathway in osteoarthritis and the role of low-density lipoprotein receptor-related protein 5 (LRP5) in human osteoarthritic chondrocytes...
  2. van Meurs J, Trikalinos T, Ralston S, Balcells S, Brandi M, Brixen K, et al. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA. 2008;299:1277-90 pubmed publisher
    Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population...
  3. Chung B, Kayserili H, Ai M, Freudenberg J, Uzumcu A, Uyguner O, et al. A mutation in the signal sequence of LRP5 in a family with an osteoporosis-pseudoglioma syndrome (OPPG)-like phenotype indicates a novel disease mechanism for trinucleotide repeats. Hum Mutat. 2009;30:641-8 pubmed publisher
    ..of phenotypes caused by mutations in the Wnt/Norrin coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) by identifying two novel types of mutation in related individuals whose presenting features were profound muscle ..
  4. Saarinen A, Välimäki V, Valimaki M, Löyttyniemi E, Auro K, Uusen P, et al. The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men. Bone. 2007;40:1006-12 pubmed
    Polymorphisms in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) contribute to variation in bone mass in the general population...
  5. Mizuguchi T, Furuta I, Watanabe Y, Tsukamoto K, Tomita H, Tsujihata M, et al. LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density. J Hum Genet. 2004;49:80-6 pubmed
    ..association study between BMD and nine candidate genes ( TGFB1, TGFBR2, SMAD2, SMAD3, SMAD4, IFNB1, IFNAR1, FOS and LRP5), as well as of a case-control study of osteoporosis...
  6. Boyden L, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick M, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002;346:1513-21 pubmed
    ..Loss-of-function mutations in the gene for low-density lipoprotein receptor-related protein 5 (LRP5), which acts in the Wnt signaling pathway, have been shown to cause osteoporosis-pseudoglioma...
  7. Shahi P, Park D, Pond A, Seethammagari M, Chiou S, Cho K, et al. Activation of Wnt signaling by chemically induced dimerization of LRP5 disrupts cellular homeostasis. PLoS ONE. 2012;7:e30814 pubmed publisher
    ..technology, we were able to modify the Wnt co-receptor, low-density lipoprotein (LDL)-receptor-related protein 5 (LRP5), to generate the synthetic ligand inducible Wnt switch, iLRP5...
  8. Ferrari S, Deutsch S, Baudoin C, Cohen Solal M, Ostertag A, Antonarakis S, et al. LRP5 gene polymorphisms and idiopathic osteoporosis in men. Bone. 2005;37:770-5 pubmed
    Mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) have demonstrated the role of LRP5 in bone mass acquisition...
  9. Mencej Bedrac S, Prezelj J, Kocjan T, Komadina R, Marc J. Analysis of association of LRP5, LRP6, SOST, DKK1, and CTNNB1 genes with bone mineral density in a Slovenian population. Calcif Tissue Int. 2009;85:501-6 pubmed publisher
    ..effects of polymorphisms in selected Wnt pathway genes: low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), Dickkopf1 (DKK1), sclerostin (SOST), and beta-catenin (CTNNB1)...
  10. Riancho J, Olmos J, Pineda B, García Ibarbia C, Pérez Núñez M, Nan D, et al. Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with replication. Eur J Endocrinol. 2011;164:123-31 pubmed publisher
    ..51 (P=0.009) and 0.47 (P<0.003) across rs11054704 and rs2302685 genotypes. In the discovery cohort, several LRP5 SNPs were associated with vertebral fractures (odds ratio (OR) 0.67; P=0...
  11. Laine C, Chung B, Susic M, Prescott T, Semler O, Fiskerstrand T, et al. Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). Eur J Hum Genet. 2011;19:875-81 pubmed publisher
    Osteoporosis-pseudoglioma sydrome (OPPG) is an autosomal recessive disorder with early-onset severe osteoporosis and blindness, caused by biallelic loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5)..
  12. Giroux S, Elfassihi L, Cardinal G, Laflamme N, Rousseau F. LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women. Bone. 2007;40:1299-307 pubmed
    ..b>LRP5 gene was previously shown to be involved in rare diseases affecting bone mass...
  13. Yang H, Li S, Xiao X, Wang P, Guo X, Zhang Q. Identification of FZD4 and LRP5 mutations in 11 of 49 families with familial exudative vitreoretinopathy. Mol Vis. 2012;18:2438-46 pubmed
    To identify mutations in FZD4 and LRP5 in 49 Chinese families with familial exudative vitreoretinopathy (FEVR) and to reveal the mutation spectrum and frequency of these genes in the Chinese population...
  14. Liu J, Zhang M, Zhao L, Cui B, Li Z, Zhao H, et al. Analysis of recently identified osteoporosis susceptibility genes in Han Chinese women. J Clin Endocrinol Metab. 2010;95:E112-20 pubmed publisher
    ..Seven SNPs in five genes [ZBTB40 (rs7524102, rs6696981), OPG (rs6993813, rs6469804), RANK (rs3018362), LRP5 (rs3736228), and SOST (rs1513670)] were found to be associated with total hip BMD...
  15. Massart F, Marini F, Bianchi G, Minisola S, Luisetto G, Pirazzoli A, et al. Genetic predictors of skeletal outcomes in healthy fertile women: the Bonturno study. Joint Bone Spine. 2013;80:414-9 pubmed publisher
    ..Low-density lipoprotein receptor-related protein 5 (LRP5) and farnesyl diphosphonate synthase (FDPS) are candidate genes for bone phenotypes...
  16. Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, et al. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13. Am J Hum Genet. 1996;59:146-51 pubmed
    Osteoporosis-pseudoglioma syndrome (OPS) is an autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness. The pathogenic mechanism is not known...
  17. Bhat B, Allen K, Liu W, Graham J, Morales A, Anisowicz A, et al. Structure-based mutation analysis shows the importance of LRP5 beta-propeller 1 in modulating Dkk1-mediated inhibition of Wnt signaling. Gene. 2007;391:103-12 pubmed
    A single point mutation (G to T) in the low-density lipoprotein receptor related protein 5 (LRP5) gene results in a glycine to valine amino acid change (G171V) and is responsible for an autosomal dominant high bone mass trait (HBM) in two ..
  18. Gong Y, Slee R, Fukai N, Rawadi G, Roman Roman S, Reginato A, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001;107:513-23 pubmed
    In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth...
  19. Little R, Carulli J, Del Mastro R, 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 pubmed
    ..amino acid change, in a predicted beta-propeller module of the low-density lipoprotein receptor-related protein 5 (LRP5), that results in the HBM phenotype...
  20. Crabbe P, Balemans W, Willaert A, Van Pottelbergh I, Cleiren E, Coucke P, et al. Missense mutations in LRP5 are not a common cause of idiopathic osteoporosis in adult men. J Bone Miner Res. 2005;20:1951-9 pubmed
    We studied whether the LRP5 gene contributes to the clinical phenotype of IO in men. Mutation analysis in 66 IO men revealed a range of sequence variants, of which two missense variants were shown to be of functional relevance...
  21. Okubo M, Horinishi A, Kim D, Yamamoto T, Murase T. Seven novel sequence variants in the human low density lipoprotein receptor related protein 5 (LRP5) gene. Hum Mutat. 2002;19:186 pubmed
    We identified seven novel polymorphisms in the human low density lipoprotein receptor related protein 5 (LRP5) gene. Two of them are predicted to replace amino acid in LRP5 protein (c.314A>G: Q89R and c...
  22. Markatseli A, Hatzi E, Bouba I, Georgiou I, Challa A, Tigas S, et al. Association of the A1330V and V667M polymorphisms of LRP5 with bone mineral density in Greek peri- and postmenopausal women. Maturitas. 2011;70:188-93 pubmed publisher
    Wnt signaling through low-density lipoprotein receptor-related protein 5 (LRP5) is an important determinant of bone mass regulation...
  23. Koh J, Jung M, Hong J, Park H, Chang J, Shin H, et al. Association between bone mineral density and LDL receptor-related protein 5 gene polymorphisms in young Korean men. J Korean Med Sci. 2004;19:407-12 pubmed
    Recently, It has been reported that the LDL receptor-related protein 5 (LRP5) regulates bone formation, and that mutations of the gene cause osteoporosis-pseudoglioma syndrome or high bone mass phenotypes...
  24. Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, et al. LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000;407:530-5 pubmed
    ..is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction...
  25. Björklund P, Akerstrom G, Westin G. An LRP5 receptor with internal deletion in hyperparathyroid tumors with implications for deregulated WNT/beta-catenin signaling. PLoS Med. 2007;4:e328 pubmed
    ..Mechanisms that may account for this activation have not been identified, except for a few cases of beta-catenin (CTNNB1) stabilizing mutation in pHPT tumors...
  26. Balemans W, Piters E, Cleiren E, Ai M, Van Wesenbeeck L, Warman M, et al. The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008;82:445-53 pubmed publisher
    Low-density lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor, plays an important role in bone metabolism as loss-of-function and gain-of-function mutations in LRP5 result in the autosomal recessive osteoporosis-pseudoglioma ..
  27. Lee Y, Woo J, Choi S, Ji J, Song G. Association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density: a meta-analysis. Rheumatol Int. 2009;29:539-44 pubmed publisher
    The association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density (BMD) has been studied, but results have been mixed...
  28. Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H. Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat. 2005;26:104-12 pubmed
    ..the genes encoding the Wnt receptor pair, frizzled 4 (FZD4) and low-density-lipoprotein receptor-related protein 5 (LRP5), have been shown to cause FEVR...
  29. Frost M, Andersen T, Gossiel F, Hansen S, Bollerslev J, Van Hul W, et al. Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5. J Bone Miner Res. 2011;26:1721-8 pubmed publisher
    Patients with an activation mutation of the Lrp5 gene exhibit high bone mass (HBM). Limited information is available regarding compartment-specific changes in bone...
  30. Hsieh J, Lee L, Zhang L, Wefer S, Brown K, DeRossi C, et al. Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell. 2003;112:355-67 pubmed
    ..MESD functions in the endoplasmic reticulum as a specific chaperone for LRP5 and LRP6, which in conjunction with Frizzled, are coreceptors for canonical WNT signal transduction...
  31. Lau H, Ng M, Ho A, Luk K, Kung A. Genetic and environmental determinants of bone mineral density in Chinese women. Bone. 2005;36:700-9 pubmed
    ..receptor (CASR), vitamin D receptor (VDR), collagen type Ialpha1 (COLIA1), and LDL receptor-related protein 5 (LRP5)...
  32. Saarinen A, Saukkonen T, Kivela T, Lahtinen U, Laine C, Somer M, et al. Low density lipoprotein receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia. Clin Endocrinol (Oxf). 2010;72:481-8 pubmed publisher
    Mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) underlie osteoporosis-pseudoglioma syndrome. Animal models implicate a role for LRP5 in lipid and glucose homeostasis...
  33. Babij P, Zhao W, Small C, Kharode Y, Yaworsky P, Bouxsein M, et al. High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res. 2003;18:960-74 pubmed
    A unique mutation in LRP5 is associated with high bone mass in man. Transgenic mice expressing this LRP5 mutation have a similar phenotype with high bone mass and enhanced strength...
  34. Koay M, Woon P, Zhang Y, Miles L, Duncan E, Ralston S, et al. Influence of LRP5 polymorphisms on normal variation in BMD. J Bone Miner Res. 2004;19:1619-27 pubmed
    Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD...
  35. Funakoshi Y, Omori H, Yada H, Katoh T. Relationship between changes of bone mineral density over seven years and A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene or lifestyle factors in Japanese female workers. Asia Pac J Clin Nutr. 2010;19:534-9 pubmed
    ..BMD) over a seven-year period and A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 (LRP5) gene or lifestyle factors...
  36. Grundberg E, Lau E, Lorentzon M, Lorentzson M, Karlsson M, Holmberg A, et al. Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men. Osteoporos Int. 2008;19:829-37 pubmed
    Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes...
  37. Qin M, Kondo H, Tahira T, Hayashi K. Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy. Hum Genet. 2008;122:615-23 pubmed
    Mutations in Norrin signaling genes (NDP, FZD4 and LRP5) have been found in patients with familial exudative vitreoretinopathy (FEVR) and the altered signaling is suspected to play a critical role in its pathogenesis...
  38. Jiang X, Chen Y, Xu L, Li X, Cao F, Li L, et al. Association of LPR5 polymorphism with bone mass density and cholesterol level in population of Chinese Han. Exp Clin Endocrinol Diabetes. 2010;118:388-91 pubmed publisher
    ..near the osteoprotegerin (OPG) gene and rs3736228 in the low-density lipoprotein receptor-related protein 5 (LRP5) gene, were found to be associated with osteoporosis and osteoporotic fractures in Caucasians in a genome wide ..
  39. 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 pubmed
    Low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor of Wnt signaling, is an important regulator of bone development and maintenance...
  40. Stathopoulou M, Dedoussis G, Trovas G, Katsalira A, Hammond N, Deloukas P, et al. Low-density lipoprotein receptor-related protein 5 polymorphisms are associated with bone mineral density in Greek postmenopausal women: an interaction with calcium intake. J Am Diet Assoc. 2010;110:1078-83 pubmed publisher
    The low-density lipoprotein receptor-related protein 5 (LRP5) has been shown to play a significant role in bone biology...
  41. Johnson M, Gong G, Kimberling W, Reckér S, Kimmel D, Recker R. Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13). Am J Hum Genet. 1997;60:1326-32 pubmed
    The purpose of this paper is to report the linkage of a genetic locus (designated "HBM") in the human genome to a phenotype of very high spinal bone density, using a single extended pedigree...
  42. Kiel D, Ferrari S, Cupples L, Karasik D, Manen D, Imamovic A, et al. Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone. 2007;40:587-96 pubmed
    Polymorphisms in the LRP5 gene have been associated with bone mineral density (BMD) in men and/or women. However, the functional basis for this association remains obscure...
  43. Bollerslev J, Wilson S, Dick I, Islam F, Ueland T, Palmer L, et al. LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women. Bone. 2005;36:599-606 pubmed
    ..The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by ..
  44. Holmen S, Salic A, Zylstra C, Kirschner M, Williams B. A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta -catenin-dependent signaling. J Biol Chem. 2002;277:34727-35 pubmed
    ..by binding to seven-transmembrane spanning receptors of the Frizzled (Fz) family together with the coreceptors LRP5 and -6, members of the low density lipoprotein receptor-related protein family (LRP)...
  45. Semenov M, Tamai K, Brott B, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001;11:951-61 pubmed
    ..Our findings suggest that Wnt-Fz-LRP6 complex formation, but not Wnt-Fz interaction, triggers Wnt/beta-catenin signaling. ..
  46. Mao J, Wang J, Liu B, Pan W, Farr G, Flynn C, et al. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell. 2001;7:801-9 pubmed
    ..In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway. ..
  47. Fretz J, Zella L, Kim S, Shevde N, Pike J. 1,25-Dihydroxyvitamin D3 regulates the expression of low-density lipoprotein receptor-related protein 5 via deoxyribonucleic acid sequence elements located downstream of the start site of transcription. Mol Endocrinol. 2006;20:2215-30 pubmed
    ..orchestrated by the Wnt signaling pathway wherein stimulation of the membrane receptor Frizzled and its coreceptor LRP5 leads to activation of beta-catenin and subsequent transcription-mediated changes in osteoblast biology...
  48. Guo Y, Xiong D, Shen H, Zhao L, Xiao P, Guo Y, et al. Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study. J Med Genet. 2006;43:798-803 pubmed
    The low-density lipoprotein receptor-related protein 5 (LRP5) gene, essential for glucose and cholesterol metabolism, may have a role in the aetiology of obesity, an important risk factor for diabetes...
  49. Ellies D, Viviano B, McCarthy J, Rey J, Itasaki N, Saunders S, et al. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res. 2006;21:1738-49 pubmed
    ..Our data suggest that functional interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate bone deposition by modulating the Wnt pathway...
  50. Brixen K, Beckers S, Peeters A, Piters E, Balemans W, Nielsen T, et al. Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with peak bone mass in non-sedentary men: results from the Odense androgen study. Calcif Tissue Int. 2007;81:421-9 pubmed
    ..exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men...
  51. Giroux S, Elfassihi L, Cole D, Rousseau F. Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women. Osteoporos Int. 2008;19:1769-75 pubmed publisher
    ..The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated...
  52. Zhang Z, Qin Y, He J, Huang Q, Li M, Hu Y, et al. Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women. Acta Pharmacol Sin. 2005;26:1111-6 pubmed
    ..possible association of Q89R, N740N and A1330V polymorphisms in low-density lipoprotein receptor-related protein 5 (LRP5) gene with bone mineral density (BMD) in postmenopausal Chinese women...
  53. Van Wesenbeeck L, Cleiren E, Gram J, Beals R, Benichou O, Scopelliti D, et al. Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet. 2003;72:763-71 pubmed
    ..The LDL receptor-related protein 5 (LRP5) gene has been shown to be involved in both osteoporosis-pseudoglioma syndrome and the high-bone-mass phenotype and ..
  54. Xu Q, Wang Y, Dabdoub A, Smallwood P, Williams J, Woods C, et al. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004;116:883-95 pubmed
    ..These data define a Norrin-Fz4 signaling system that plays a central role in vascular development in the eye and ear, and they indicate that ligands unrelated to Wnts can act through Fz receptors. ..
  55. Nikopoulos K, Venselaar H, Collin R, Riveiro Alvarez R, Boonstra F, Hooymans J, et al. Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP. Hum Mutat. 2010;31:656-66 pubmed publisher
    ..Mutations in the genes encoding the low density lipoprotein receptor protein 5 (LRP5) and frizzled 4 (FZD4), acting as coreceptors for Wnt ligands, cause familial exudative vitreoretinopathy (FEVR)...
  56. Urano T, Shiraki M, Usui T, Sasaki N, Ouchi Y, Inoue S. A1330V variant of the low-density lipoprotein receptor-related protein 5 (LRP5) gene decreases Wnt signaling and affects the total body bone mineral density in Japanese women. Endocr J. 2009;56:625-31 pubmed
    ..The Wnt co-receptor, namely, low-density lipoprotein receptor-related protein 5 (LRP5), initiates Wnt signal transduction...
  57. Urano T, Shiraki M, Ezura Y, Fujita M, Sekine E, Hoshino S, et al. Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J Bone Miner Metab. 2004;22:341-5 pubmed
    Low-density lipoprotein receptor-related protein 5 (LRP5) is an important regulator of osteoblast growth and differentiation, affecting peak bone mass in vertebrates...
  58. Berwick D, Harvey K. The importance of Wnt signalling for neurodegeneration in Parkinson's disease. Biochem Soc Trans. 2012;40:1123-8 pubmed
    ..This suggests the prospect of targeting Wnt signalling pathways to modify PD progression. ..
  59. Papathanasiou I, Malizos K, Tsezou A. Bone morphogenetic protein-2-induced Wnt/?-catenin signaling pathway activation through enhanced low-density-lipoprotein receptor-related protein 5 catabolic activity contributes to hypertrophy in osteoarthritic chondrocytes. Arthritis Res Ther. 2012;14:R82 pubmed publisher
    ..Our findings suggest, for the first time to our knowledge, that BMP-2-induced Wnt/?-catenin signaling activation through LRP-5 may contribute to chondrocyte hypertrophy and cartilage degradation in osteoarthritis. ..
  60. Xiong D, Lei S, Yang F, Wang L, Peng Y, Wang W, et al. Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. J Bone Miner Res. 2007;22:385-93 pubmed
    In this study, the associations of novel LRP5 variants with BMD variation were detected and some replicated in the two ethnic groups of Chinese and white origins, respectively...
  61. Ferrari S, Deutsch S, Choudhury U, Chevalley T, Bonjour J, Dermitzakis E, et al. Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet. 2004;74:866-75 pubmed
    ..and stature at chromosome 11q12-13, a region harboring the low-density lipoprotein receptor-related protein 5 (LRP5) gene...
  62. Falcón Ramírez E, Casas Avila L, Cerda Flores R, Castro Hernández C, Rubio Lightbourn J, Velázquez Cruz R, et al. Association of LRP5 haplotypes with osteoporosis in Mexican women. Mol Biol Rep. 2013;40:2705-10 pubmed publisher
    ..G/A rs4988321, T/C rs627174 and T/C rs901824) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) and their association with osteoporosis in 100 pos-menopausal osteoporotic Mexican women and their controls, using ..
  63. Jiao X, Ventruto V, Trese M, Shastry B, Hejtmancik J. Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am J Hum Genet. 2004;75:878-84 pubmed
    ..This region contains LRP5 but not FZD4; mutations in both of these genes cause autosomal dominant FEVR...
  64. Koller D, Ichikawa S, Johnson M, Lai D, Xuei X, Edenberg H, et al. Contribution of the LRP5 gene to normal variation in peak BMD in women. J Bone Miner Res. 2005;20:75-80 pubmed
    The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD...
  65. Ai M, Holmen S, Van Hul W, Williams B, Warman M. 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;25:4946-55 pubmed
    The low-density-lipoprotein receptor-related protein 5 (LRP5), a coreceptor in the canonical Wnt signaling pathway, has been implicated in human disorders of low and high bone mass...
  66. Guo J, Cooper L. Influence of an LRP5 cytoplasmic SNP on Wnt signaling and osteoblastic differentiation. Bone. 2007;40:57-67 pubmed
    The low density lipoprotein receptor-related protein 5 (LRP5) is a key determinant of bone mass, via the Wnt signaling pathway control of osteoblast function...
  67. Richards J, Rivadeneira F, Inouye M, Pastinen T, Soranzo N, Wilson S, et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet. 2008;371:1505-12 pubmed publisher
    ..rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene...
  68. Furuya T, Urano T, Ikari K, Kotake S, Inoue S, Hara M, et al. A1330V polymorphism of low-density lipoprotein receptor-related protein 5 gene and self-reported incident fractures in Japanese female patients with rheumatoid arthritis. Mod Rheumatol. 2009;19:140-6 pubmed publisher
    We attempted to determine whether the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 (LRP5) gene is associated with a risk of self-reported incident fractures and hypercholesterolemia in Japanese patients ..
  69. Tran B, Nguyen N, Eisman J, Nguyen T. Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis. BMC Med Genet. 2008;9:55 pubmed publisher
    The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in BMD in high bone mass pedigrees...
  70. van Meurs J, Rivadeneira F, Jhamai M, Hugens W, Hofman A, van Leeuwen J, et al. Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. J Bone Miner Res. 2006;21:141-50 pubmed
    Both LRP5 and LRP6 genes have been implicated to play a role in bone metabolism. In a large population-based study, we related common variation in both genes to bone parameters and fractures...
  71. Li Z, Yang J, Vazquez E, Rose D, Vakar Lopez F, Mathew P, et al. Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone. Oncogene. 2008;27:596-603 pubmed
    ..MDA PCa 2b cells did not induce bone formation in calvaria from mice lacking the Wnt co-receptor Lrp5. In human specimens, WNT7b was not expressed in normal prostate but was expressed in areas of high-grade prostate ..
  72. Hey P, Twells R, Phillips M, Yusuke Nakagawa -, Brown S, Kawaguchi Y, et al. Cloning of a novel member of the low-density lipoprotein receptor family. Gene. 1998;216:103-11 pubmed
    ..The gene, termed low-density lipoprotein receptor related protein 5 (LRP5), encodes a protein of 1615 amino acids that contains conserved modules which are characteristic of the low-density ..
  73. de Crecchio G, Simonelli F, Nunziata G, Mazzeo S, Greco G, Rinaldi E, et al. Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity. Clin Genet. 1998;54:315-20 pubmed
    ..Compared with the other modes of inheritance, the inherited clinical features here include earlier onset (at birth) and a more severe progressive course. ..
  74. Wang K, Zhang Y, Li X, Chen L, Wang H, Wu J, et al. Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism. J Biol Chem. 2008;283:23371-5 pubmed publisher
    ..These results suggest that Kremen may not be essential for Dkk1-mediated Wnt antagonism and that Kremen may only play a role when cells express a high level of LRP5/6.
  75. Ahn V, Chu M, Choi H, Tran D, Abo A, Weis W. Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev Cell. 2011;21:862-73 pubmed publisher
    LDL receptor-related proteins 5 and 6 (LRP5/6) are coreceptors for Wnt growth factors, and also bind Dkk proteins, secreted inhibitors of Wnt signaling. The LRP5/6 ectodomain contains four β-propeller/EGF-like domain repeats...
  76. Bafico A, Liu G, Yaniv A, Gazit A, Aaronson S. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol. 2001;3:683-6 pubmed
  77. Fujino T, Asaba H, Kang M, Ikeda Y, Sone H, Takada S, et al. Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A. 2003;100:229-34 pubmed
    A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays an essential role in bone accrual and eye development. Here, we show that LRP5 is also required for normal cholesterol and glucose metabolism...
  78. Toomes C, Bottomley H, Jackson R, Towns K, Scott S, Mackey D, et al. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet. 2004;74:721-30 pubmed
    ..Here, we describe mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor...
  79. Piao S, Lee S, Kim H, Yum S, Stamos J, Xu Y, et al. Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling. PLoS ONE. 2008;3:e4046 pubmed publisher
    ..These observations demonstrate that phosphorylated LRP6/5 both recruits and directly inhibits GSK3beta using two distinct portions of its cytoplasmic sequence, and suggest a novel mechanism of activation in this signaling pathway. ..
  80. Smith A, Gidley J, Sandy J, Perry M, Elson C, Kirwan J, et al. Haplotypes of the low-density lipoprotein receptor-related protein 5 (LRP5) gene: are they a risk factor in osteoarthritis?. Osteoarthritis Cartilage. 2005;13:608-13 pubmed
    ..locus on chromosome 11q in close proximity to the low-density lipoprotein receptor-related protein 5 (LRP5) gene...
  81. Bourhis E, Tam C, Franke Y, Bazan J, Ernst J, Hwang J, et al. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 2010;285:9172-9 pubmed publisher
    ..of secreted Wnt with its receptors Frizzled (Fz) and low density lipoprotein receptor-related protein 5/6 (LRP5/6)...