Mutations in LRP5 cause primary osteoporosis without features of OI by reducing Wnt signaling activity

go back to reference Rauch F, Travers R, Norman ME, Taylor A, Parfitt AM, Glorieux FH: Deficient bone formation in idiopathic juvenile osteoporosis: a histomorphometric study of cancellous iliac bone. J Bone Miner Res. 2000, 15 (5): 957-963.CrossRefPubMed Rauch F, Travers R, Norman ME, Taylor A, Parfitt AM, Glorieux FH: Deficient bone formation in idiopathic juvenile osteoporosis: a histomorphometric study of cancellous iliac bone. J Bone Miner Res. 2000, 15 (5): 957-963.CrossRefPubMed

go back to reference Rauch F, Travers R, Norman ME, Taylor A, Parfitt AM, Glorieux FH: The bone formation defect in idiopathic juvenile osteoporosis is surface-specific. Bone. 2002, 31 (1): 85-89. 10.1016/S8756-3282(02)00814-1.CrossRefPubMed Rauch F, Travers R, Norman ME, Taylor A, Parfitt AM, Glorieux FH: The bone formation defect in idiopathic juvenile osteoporosis is surface-specific. Bone. 2002, 31 (1): 85-89. 10.1016/S8756-3282(02)00814-1.CrossRefPubMed

go back to reference Lorenc RS: Idiopathic juvenile osteoporosis. Calcif Tissue Int. 2002, 70 (5): 395-397. 10.1007/s00223-001-0045-y.CrossRefPubMed Lorenc RS: Idiopathic juvenile osteoporosis. Calcif Tissue Int. 2002, 70 (5): 395-397. 10.1007/s00223-001-0045-y.CrossRefPubMed

go back to reference Hartikka H, Mäkitie O, Männikkö M, Doria AS, Daneman A, Cole WG, Ala-Kokko L, Sochett EB: Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children. J Bone Miner Res. 2005, 20 (5): 783-789. 10.1359/JBMR.050101.CrossRefPubMed Hartikka H, Mäkitie O, Männikkö M, Doria AS, Daneman A, Cole WG, Ala-Kokko L, Sochett EB: Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children. J Bone Miner Res. 2005, 20 (5): 783-789. 10.1359/JBMR.050101.CrossRefPubMed

go back to reference Cadigan KM, Nusse R: Wnt signaling: a common theme in animal development. Genes Dev. 1997, 11 (24): 3286-3305. 10.1101/gad.11.24.3286.CrossRefPubMed Cadigan KM, Nusse R: Wnt signaling: a common theme in animal development. Genes Dev. 1997, 11 (24): 3286-3305. 10.1101/gad.11.24.3286.CrossRefPubMed

go back to reference Westendorf JJ, Kahler RA, Schroeder TM: Wnt signaling in osteoblasts and bone diseases. Gene. 2004, 341: 19-39.CrossRefPubMed Westendorf JJ, Kahler RA, Schroeder TM: Wnt signaling in osteoblasts and bone diseases. Gene. 2004, 341: 19-39.CrossRefPubMed

go back to reference Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP: High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002, 346 (20): 1513-1521. 10.1056/NEJMoa013444.CrossRefPubMed Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP: High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002, 346 (20): 1513-1521. 10.1056/NEJMoa013444.CrossRefPubMed

go back to reference Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML: 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): 11-19. 10.1086/338450.CrossRefPubMed Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, FitzGerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML: 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): 11-19. 10.1086/338450.CrossRefPubMed

go back to reference Levasseur R, Lacombe D, de Vernejoul MC: LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint, Bone, Spine. 2005, 72 (3): 207-214. 10.1016/j.jbspin.2004.10.008.CrossRefPubMed Levasseur R, Lacombe D, de Vernejoul MC: LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint, Bone, Spine. 2005, 72 (3): 207-214. 10.1016/j.jbspin.2004.10.008.CrossRefPubMed

go back to reference Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GCM, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Jüppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML: Osteoporosis-Pseudoglioma Syndrome Collaborative group: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001, 107 (4): 513-523. 10.1016/S0092-8674(01)00571-2.CrossRefPubMed Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GCM, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Jüppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML: Osteoporosis-Pseudoglioma Syndrome Collaborative group: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001, 107 (4): 513-523. 10.1016/S0092-8674(01)00571-2.CrossRefPubMed

go back to reference Ai M, Heeger S, Bartels CF, Schelling DK: Osteoporosis-Pseudoglioma Collaborative group: Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet. 2005, 77 (5): 741-753. 10.1086/497706.CrossRefPubMedPubMedCentral Ai M, Heeger S, Bartels CF, Schelling DK: Osteoporosis-Pseudoglioma Collaborative group: Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet. 2005, 77 (5): 741-753. 10.1086/497706.CrossRefPubMedPubMedCentral

go back to reference Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA: Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L: 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): 303-314. 10.1083/jcb.200201089.CrossRefPubMedPubMedCentral Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA: Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L: 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): 303-314. 10.1083/jcb.200201089.CrossRefPubMedPubMedCentral

go back to reference Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Bénichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, de Vernejoul MC, Bollerslev J, Van Hul W: 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 (3): 763-771. 10.1086/368277.CrossRefPubMedPubMedCentral Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Bénichou O, Scopelliti D, Key L, Renton T, Bartels C, Gong Y, Warman ML, de Vernejoul MC, Bollerslev J, Van Hul W: 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 (3): 763-771. 10.1086/368277.CrossRefPubMedPubMedCentral

go back to reference Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, Rizzoli R, Antonarakis SE: 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 (5): 866-875. 10.1086/420771.CrossRefPubMedPubMedCentral Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, Rizzoli R, Antonarakis SE: 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 (5): 866-875. 10.1086/420771.CrossRefPubMedPubMedCentral

go back to reference Koay MA, Woon PY, Zhang Y, Miles LJ, Duncan EL, Ralston SH, Compston JE, Cooper C, Keen R, Langdahl BL, MacLelland A, O'Riordan J, Pols HA, Reid DM, Uitterlinden AG, Wass JA, Brown MA: Influence of LRP5 polymorphisms on normal variation in BMD. J Bone Miner Res. 2004, 19 (10): 1619-1627. 10.1359/JBMR.040704.CrossRefPubMed Koay MA, Woon PY, Zhang Y, Miles LJ, Duncan EL, Ralston SH, Compston JE, Cooper C, Keen R, Langdahl BL, MacLelland A, O'Riordan J, Pols HA, Reid DM, Uitterlinden AG, Wass JA, Brown MA: Influence of LRP5 polymorphisms on normal variation in BMD. J Bone Miner Res. 2004, 19 (10): 1619-1627. 10.1359/JBMR.040704.CrossRefPubMed

go back to reference Hey PJ, Twells RC, Phillips MS, Nakagawa Y, Brown SD, Kawaguchi Y, Cox R, Xie G, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF: Cloning of a novel member of the low-density lipoprotein receptor family. Gene. 1998, 216 (1): 103-111. 10.1016/S0378-1119(98)00311-4.CrossRefPubMed Hey PJ, Twells RC, Phillips MS, Nakagawa Y, Brown SD, Kawaguchi Y, Cox R, Xie G, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF: Cloning of a novel member of the low-density lipoprotein receptor family. Gene. 1998, 216 (1): 103-111. 10.1016/S0378-1119(98)00311-4.CrossRefPubMed

go back to reference Yadav VK, Ryu JH, Suda N, Tanaka K, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G: Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008, 135 (5): 825-837. 10.1016/j.cell.2008.09.059.CrossRefPubMedPubMedCentral Yadav VK, Ryu JH, Suda N, Tanaka K, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G: Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008, 135 (5): 825-837. 10.1016/j.cell.2008.09.059.CrossRefPubMedPubMedCentral

go back to reference 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. 2010, 46 (1): 4-12. 10.1016/j.bone.2009.06.029.CrossRefPubMed 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. 2010, 46 (1): 4-12. 10.1016/j.bone.2009.06.029.CrossRefPubMed

go back to reference Cui Y, Niziolek PJ, Macdonald BT, Zylstra CR, Alenina N, Robinson DR, Zhong C, Matthes S, Jacobsen CM, Conlon RA, Brommage R, Liu Q, Mseeh F, Powell DR, Yang Q, Zambrowicz B, Gerrits H, Gossen JA, He X, Bader M, Williams BO, Warman ML, Robling AG: Lrp5 functions in bone to regulate bone mass. Nat Med. 2011, 17 (6): 684-691.CrossRefPubMedPubMedCentral Cui Y, Niziolek PJ, Macdonald BT, Zylstra CR, Alenina N, Robinson DR, Zhong C, Matthes S, Jacobsen CM, Conlon RA, Brommage R, Liu Q, Mseeh F, Powell DR, Yang Q, Zambrowicz B, Gerrits H, Gossen JA, He X, Bader M, Williams BO, Warman ML, Robling AG: Lrp5 functions in bone to regulate bone mass. Nat Med. 2011, 17 (6): 684-691.CrossRefPubMedPubMedCentral

go back to reference Ward LMGF: The spectrum of pediatric osteoporosis. Pediatric bone. Biology and diseases. Edited by: Glorieux FH, Pettifor JM, Jüppner H. 2003, San Diego: Academic Press, 401-442. 1CrossRef Ward LMGF: The spectrum of pediatric osteoporosis. Pediatric bone. Biology and diseases. Edited by: Glorieux FH, Pettifor JM, Jüppner H. 2003, San Diego: Academic Press, 401-442. 1CrossRef

go back to reference den Dunnen JT, Antonarakis SE: Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat. 2000, 15 (1): 7-12. 10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N.CrossRefPubMed den Dunnen JT, Antonarakis SE: Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat. 2000, 15 (1): 7-12. 10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N.CrossRefPubMed

go back to reference Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002, 30 (12): e57-10.1093/nar/gnf056.CrossRefPubMedPubMedCentral Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002, 30 (12): e57-10.1093/nar/gnf056.CrossRefPubMedPubMedCentral

go back to reference 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): 4946-4955. 10.1128/MCB.25.12.4946-4955.2005.CrossRefPubMedPubMedCentral 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): 4946-4955. 10.1128/MCB.25.12.4946-4955.2005.CrossRefPubMedPubMedCentral

go back to reference Livak KJ, Schmittgen TD: Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ΔΔC T Method. Methods. 2001, 25 (4): 402-408. 10.1006/meth.2001.1262.CrossRefPubMed Livak KJ, Schmittgen TD: Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2^-ΔΔC _T Method. Methods. 2001, 25 (4): 402-408. 10.1006/meth.2001.1262.CrossRefPubMed

go back to reference Laine CM, Chung BD, Susic M, Prescott T, Semler O, Fiskerstrand T, D'Eufemia P, Castori M, Pekkinen M, Sochett E, Cole WG, Netzer C, Mäkitie O: Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). Eur J Hum Genet. 2011, 19 (8): 875-881. 10.1038/ejhg.2011.42.CrossRefPubMedPubMedCentral Laine CM, Chung BD, Susic M, Prescott T, Semler O, Fiskerstrand T, D'Eufemia P, Castori M, Pekkinen M, Sochett E, Cole WG, Netzer C, Mäkitie O: Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). Eur J Hum Genet. 2011, 19 (8): 875-881. 10.1038/ejhg.2011.42.CrossRefPubMedPubMedCentral

go back to reference Wang B, Sinha T, Jiao K, Serra R, Wang J: Disruption of PCP signaling causes limb morphogenesis and skeletal defects and may underlie Robinow syndrome and brachydactyly type B. Hum Mol Genet. 2011, 20 (2): 271-285. 10.1093/hmg/ddq462.CrossRefPubMed Wang B, Sinha T, Jiao K, Serra R, Wang J: Disruption of PCP signaling causes limb morphogenesis and skeletal defects and may underlie Robinow syndrome and brachydactyly type B. Hum Mol Genet. 2011, 20 (2): 271-285. 10.1093/hmg/ddq462.CrossRefPubMed

go back to reference Mejia-Gaviria N, Gil-Peña H, Coto E, Pérez-Menéndez TM, Santos F: Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: a case report. Orphanet J Rare Dis. 2010, 5: 1-10.1186/1750-1172-5-1.CrossRefPubMedPubMedCentral Mejia-Gaviria N, Gil-Peña H, Coto E, Pérez-Menéndez TM, Santos F: Genetic and clinical peculiarities in a new family with hereditary hypophosphatemic rickets with hypercalciuria: a case report. Orphanet J Rare Dis. 2010, 5: 1-10.1186/1750-1172-5-1.CrossRefPubMedPubMedCentral

go back to reference Morón FJ, Mendoza N, Vázquez F, Molero E, Quereda F, Salinas A, Fontes J, Martinez-Astorquiza T, Sánchez-Borrego R, Ruiz A: Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis. Bone. 2006, 39 (1): 213-221. 10.1016/j.bone.2005.12.079.CrossRefPubMed Morón FJ, Mendoza N, Vázquez F, Molero E, Quereda F, Salinas A, Fontes J, Martinez-Astorquiza T, Sánchez-Borrego R, Ruiz A: Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis. Bone. 2006, 39 (1): 213-221. 10.1016/j.bone.2005.12.079.CrossRefPubMed

go back to reference Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X: LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000, 407 (6803): 530-535. 10.1038/35035117.CrossRefPubMed Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X: LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000, 407 (6803): 530-535. 10.1038/35035117.CrossRefPubMed

go back to reference Ettenberg SA, Charlat O, Daley MP, Liu S, Vincent KJ, Stuart DD, Schuller AG, Yuan J, Ospina B, Green J, Yu Q, Walsh R, Li S, Schmitz R, Heine H, Bilic S, Ostrom L, Mosher R, Hartlepp KF, Zhu Z, Fawell S, Yao YM, Stover D, Finan PM, Porter JA, Sellers WR, Klagge IM, Cong F: Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies. Proc Natl Acad Sci USA. 2010, 107 (35): 15473-15478. 10.1073/pnas.1007428107.CrossRefPubMedPubMedCentral Ettenberg SA, Charlat O, Daley MP, Liu S, Vincent KJ, Stuart DD, Schuller AG, Yuan J, Ospina B, Green J, Yu Q, Walsh R, Li S, Schmitz R, Heine H, Bilic S, Ostrom L, Mosher R, Hartlepp KF, Zhu Z, Fawell S, Yao YM, Stover D, Finan PM, Porter JA, Sellers WR, Klagge IM, Cong F: Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies. Proc Natl Acad Sci USA. 2010, 107 (35): 15473-15478. 10.1073/pnas.1007428107.CrossRefPubMedPubMedCentral

go back to reference Bourhis E, Tam C, Franke Y, Bazan JF, Ernst J, Hwang J, Costa M, Cochran AG, Hannoush RN: Reconstitution of a frizzled8. Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 2010, 285 (12): 9172-9179. 10.1074/jbc.M109.092130.CrossRefPubMedPubMedCentral Bourhis E, Tam C, Franke Y, Bazan JF, Ernst J, Hwang J, Costa M, Cochran AG, Hannoush RN: Reconstitution of a frizzled8. Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 2010, 285 (12): 9172-9179. 10.1074/jbc.M109.092130.CrossRefPubMedPubMedCentral

go back to reference Itasaki N, Jones CM, Mercurio S, Rowe A, Domingos PM, Smith JC, Krumlauf R: Wise, a context-dependent activator and inhibitor of Wnt signalling. Development. 2003, 130 (18): 4295-4305. 10.1242/dev.00674.CrossRefPubMed Itasaki N, Jones CM, Mercurio S, Rowe A, Domingos PM, Smith JC, Krumlauf R: Wise, a context-dependent activator and inhibitor of Wnt signalling. Development. 2003, 130 (18): 4295-4305. 10.1242/dev.00674.CrossRefPubMed

go back to reference Semënov M, Tamai K, He X: SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005, 280 (29): 26770-26775. 10.1074/jbc.M504308200.CrossRefPubMed Semënov M, Tamai K, He X: SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005, 280 (29): 26770-26775. 10.1074/jbc.M504308200.CrossRefPubMed

go back to reference Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C: LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001, 411 (6835): 321-325. 10.1038/35077108.CrossRefPubMed Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C: LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001, 411 (6835): 321-325. 10.1038/35077108.CrossRefPubMed

go back to reference Bourhis E, Wang W, Tam C, Hwang J, Zhang Y, Spittler D, Huang OW, Gong Y, Estevez A, Zilberleyb I, Rouge L, Chiu C, Wu Y, Costa M, Hannoush RN, Franke Y, Cochran AG: Wnt antagonists bind through a short peptide to the first β-propeller domain of LRP5/6. Structure. 2011, 19 (10): 1433-1442.CrossRefPubMed Bourhis E, Wang W, Tam C, Hwang J, Zhang Y, Spittler D, Huang OW, Gong Y, Estevez A, Zilberleyb I, Rouge L, Chiu C, Wu Y, Costa M, Hannoush RN, Franke Y, Cochran AG: Wnt antagonists bind through a short peptide to the first β-propeller domain of LRP5/6. Structure. 2011, 19 (10): 1433-1442.CrossRefPubMed

go back to reference Ahn VE, Chu ML, Choi HJ, Tran D, Abo A, Wes WI: Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev Cell. 2011, 21 (5): 862-873.CrossRefPubMedPubMedCentral Ahn VE, Chu ML, Choi HJ, Tran D, Abo A, Wes WI: Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6. Dev Cell. 2011, 21 (5): 862-873.CrossRefPubMedPubMedCentral

go back to reference Li Y, Lu W, King TD, Liu CC, Bijur GN, Bu G: Dkk1 stabilizes Wnt co-receptor LRP6: implication for Wnt ligand-induced LRP6 down-regulation. PLoS One. 2010, 5 (6): e11014-10.1371/journal.pone.0011014.CrossRefPubMedPubMedCentral Li Y, Lu W, King TD, Liu CC, Bijur GN, Bu G: Dkk1 stabilizes Wnt co-receptor LRP6: implication for Wnt ligand-induced LRP6 down-regulation. PLoS One. 2010, 5 (6): e11014-10.1371/journal.pone.0011014.CrossRefPubMedPubMedCentral

go back to reference Saarinen A, Saukkonen T, Kivelä T, Lahtinen U, Laine C, Somer M, Toiviainen-Salo S, Cole WG, Lehesjoki AE, Mäkitie O: Low density lipoprotein receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia. Clin Endocrinol (Oxf). 2010, 72 (4): 481-488. 10.1111/j.1365-2265.2009.03680.x.CrossRef Saarinen A, Saukkonen T, Kivelä T, Lahtinen U, Laine C, Somer M, Toiviainen-Salo S, Cole WG, Lehesjoki AE, Mäkitie O: Low density lipoprotein receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia. Clin Endocrinol (Oxf). 2010, 72 (4): 481-488. 10.1111/j.1365-2265.2009.03680.x.CrossRef

go back to reference Cheng Z, Biechele T, Wei Z, Morrone S, Moon RT, Wang L, Xu W: : Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat Struct Mol Biol. 2011, 18(11):1204-1210., 18 (11): 1204-1210.CrossRefPubMedPubMedCentral Cheng Z, Biechele T, Wei Z, Morrone S, Moon RT, Wang L, Xu W: : Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat Struct Mol Biol. 2011, 18(11):1204-1210., 18 (11): 1204-1210.CrossRefPubMedPubMedCentral

go back to reference Balemans W, Devogelaer JP, Cleiren E, Piters E, Caussin E, Van Hul W: Novel LRP5 missense mutation in a patient with a high bone mass phenotype results in decreased DKK1-mediated inhibition of Wnt signaling. J Bone Miner Res. 2007, 22 (5): 708-716. 10.1359/jbmr.070211.CrossRefPubMed Balemans W, Devogelaer JP, Cleiren E, Piters E, Caussin E, Van Hul W: Novel LRP5 missense mutation in a patient with a high bone mass phenotype results in decreased DKK1-mediated inhibition of Wnt signaling. J Bone Miner Res. 2007, 22 (5): 708-716. 10.1359/jbmr.070211.CrossRefPubMed

go back to reference Balemans W, Piters E, Cleiren E, Ai M, Wesenbeeck LV, Warman ML, Van Hul W: The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008, 82 (6): 445-453. 10.1007/s00223-008-9130-9.CrossRefPubMed Balemans W, Piters E, Cleiren E, Ai M, Wesenbeeck LV, Warman ML, Van Hul W: The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008, 82 (6): 445-453. 10.1007/s00223-008-9130-9.CrossRefPubMed

go back to reference 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 (4): 625-631. 10.1507/endocrj.K09E-133.CrossRefPubMed 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 (4): 625-631. 10.1507/endocrj.K09E-133.CrossRefPubMed

go back to reference Crabbe P, Balemans W, Willaert A, Van Pottelbergh I, Cleiren E, Coucke PJ, Ai M, Goemaere S, Van Hul W, De Paepe A, Kaufman JM: Missense mutations in LRP5 are not a common cause of idiopathic osteoporosis in adult men. J Bone Miner Res. 2005, 20 (11): 1951-1959. 10.1359/JBMR.050705.CrossRefPubMed Crabbe P, Balemans W, Willaert A, Van Pottelbergh I, Cleiren E, Coucke PJ, Ai M, Goemaere S, Van Hul W, De Paepe A, Kaufman JM: Missense mutations in LRP5 are not a common cause of idiopathic osteoporosis in adult men. J Bone Miner Res. 2005, 20 (11): 1951-1959. 10.1359/JBMR.050705.CrossRefPubMed

go back to reference Narayan G, Bourdon V, Chaganti S, Arias-Pulido H, Nandula SV, Rao PH, Gissmann L, Dürst M, Schneider A, Pothuri B, Mansukhani M, Basso K, Chaganti RS, Murty VV: Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. Genes Chromosomes Cancer. 2007, 46 (4): 373-384. 10.1002/gcc.20418.CrossRefPubMed Narayan G, Bourdon V, Chaganti S, Arias-Pulido H, Nandula SV, Rao PH, Gissmann L, Dürst M, Schneider A, Pothuri B, Mansukhani M, Basso K, Chaganti RS, Murty VV: Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. Genes Chromosomes Cancer. 2007, 46 (4): 373-384. 10.1002/gcc.20418.CrossRefPubMed

go back to reference Tone AA, Begley H, Sharma M, Murphy J, Rosen B, Brown TJ, Shaw PA: Gene expression profiles of luteal phase fallopian tube epithelium from BRCA mutation carriers resemble high-grade serous carcinoma. Clin Cancer Res. 2008, 14 (13): 4067-4078. 10.1158/1078-0432.CCR-07-4959.CrossRefPubMed Tone AA, Begley H, Sharma M, Murphy J, Rosen B, Brown TJ, Shaw PA: Gene expression profiles of luteal phase fallopian tube epithelium from BRCA mutation carriers resemble high-grade serous carcinoma. Clin Cancer Res. 2008, 14 (13): 4067-4078. 10.1158/1078-0432.CCR-07-4959.CrossRefPubMed

go back to reference Lee B, Du H, Taylor HS: Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol Reprod. 2009, 80 (1): 79-85. 10.1095/biolreprod.108.070391.CrossRefPubMedPubMedCentral Lee B, Du H, Taylor HS: Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol Reprod. 2009, 80 (1): 79-85. 10.1095/biolreprod.108.070391.CrossRefPubMedPubMedCentral

go back to reference Margarit L, Taylor A, Roberts MH, Hopkins L, Davies C, Brenton AG, Conlan RS, Bunkheila A, Joels L, White JO, Gonzalez D: MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. J Clin Endocrinol Metab. 2010, 95 (12): 5320-5329. 10.1210/jc.2010-0603.CrossRefPubMed Margarit L, Taylor A, Roberts MH, Hopkins L, Davies C, Brenton AG, Conlan RS, Bunkheila A, Joels L, White JO, Gonzalez D: MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. J Clin Endocrinol Metab. 2010, 95 (12): 5320-5329. 10.1210/jc.2010-0603.CrossRefPubMed

go back to reference Sadek KH, Cagampang FR, Bruce KD, Shreeve N, Macklon N, Cheong Y: Variation in stability of housekeeping genes in endometrium of healthy and polycystic ovarian syndrome women. Hum Reprod. 2011. Sadek KH, Cagampang FR, Bruce KD, Shreeve N, Macklon N, Cheong Y: Variation in stability of housekeeping genes in endometrium of healthy and polycystic ovarian syndrome women. Hum Reprod. 2011.

go back to reference Cui Y, Niziolek PJ, Macdonald BT, Zylstra CR, Alenina N, Robinson DR, Zhong Z, Matthes S, Jacobsen CM, Conlon RA, Brommage R, Liu Q, Mseeh F, Powell DR, Yang QM, Zambrowicz B, Gerrits H, Gossen JA, He X, Bader M, Williams BO, Warman ML, Robling AG: Lrp5 functions in bone to regulate bone mass. Nat Med. 2011, 17 (6): 684-691. 10.1038/nm.2388.CrossRefPubMedPubMedCentral Cui Y, Niziolek PJ, Macdonald BT, Zylstra CR, Alenina N, Robinson DR, Zhong Z, Matthes S, Jacobsen CM, Conlon RA, Brommage R, Liu Q, Mseeh F, Powell DR, Yang QM, Zambrowicz B, Gerrits H, Gossen JA, He X, Bader M, Williams BO, Warman ML, Robling AG: Lrp5 functions in bone to regulate bone mass. Nat Med. 2011, 17 (6): 684-691. 10.1038/nm.2388.CrossRefPubMedPubMedCentral

go back to reference Semënov 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): 38276-38284. 10.1074/jbc.M609509200.CrossRefPubMed Semënov 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): 38276-38284. 10.1074/jbc.M609509200.CrossRefPubMed

go back to reference Piters E, Culha C, Moester M, Van Bezooijen R, Adriaensen D, Mueller T, Weidauer S, Jennes K, de Freitas F, Löwik C, Timmermans JP, Van Hul W, Papapoulos S: First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function. Hum Mutat. 2010, 31 (7): E1526-E1543. 10.1002/humu.21274.CrossRefPubMed Piters E, Culha C, Moester M, Van Bezooijen R, Adriaensen D, Mueller T, Weidauer S, Jennes K, de Freitas F, Löwik C, Timmermans JP, Van Hul W, Papapoulos S: First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function. Hum Mutat. 2010, 31 (7): E1526-E1543. 10.1002/humu.21274.CrossRefPubMed

go back to reference Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD: The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med. 2003, 349 (26): 2483-2494. 10.1056/NEJMoa030847.CrossRefPubMed Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD: The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med. 2003, 349 (26): 2483-2494. 10.1056/NEJMoa030847.CrossRefPubMed

go back to reference Qiang YW, Barlogie B, Rudikoff S, Shaughnessy JD: Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone. 2008, 42 (4): 669-680. 10.1016/j.bone.2007.12.006.CrossRefPubMed Qiang YW, Barlogie B, Rudikoff S, Shaughnessy JD: Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone. 2008, 42 (4): 669-680. 10.1016/j.bone.2007.12.006.CrossRefPubMed