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Article

Wnt-Lrp5 Signaling Regulates Fatty Acid Metabolism in the Osteoblast

, , , , , , , & show all
Pages 1979-1991 | Received 05 Nov 2014, Accepted 16 Mar 2015, Published online: 20 Mar 2023

REFERENCES

  • Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C. 2005. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell 8:727–738. http://dx.doi.org/10.1016/j.devcel.2005.02.013.
  • Glass DA, II, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G. 2005. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764. http://dx.doi.org/10.1016/j.devcel.2005.02.017.
  • MacDonald BT, Tamai K, He X. 2009. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26. http://dx.doi.org/10.1016/j.devcel.2009.06.016.
  • Regard JB, Zhong Z, Williams BO, Yang Y. 2012. Wnt signaling in bone development and disease: making stronger bone with Wnts. Cold Spring Harbor Perspect Biol 4:a007997. http://dx.doi.org/10.1101/cshperspect.a007997.
  • Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC, Bouxsein ML, Deng L, Clemens TL, Williams BO. 2005. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem 280:21162–21168. http://dx.doi.org/10.1074/jbc.M501900200.
  • Riddle RC, Diegel CR, Leslie JM, Van Koevering KK, Faugere MC, Clemens TL, Williams BO. 2013. Lrp5 and Lrp6 exert overlapping functions in osteoblasts during postnatal bone acquisition. PLoS One 8:e63323. http://dx.doi.org/10.1371/journal.pone.0063323.
  • Zhong Z, Zylstra-Diegel CR, Schumacher CA, Baker JJ, Carpenter AC, Rao S, Yao W, Guan M, Helms JA, Lane NE, Lang RA, Williams BO. 2012. Wntless functions in mature osteoblasts to regulate bone mass. Proc Natl Acad Sci U S A 109:E2197–E2204. http://dx.doi.org/10.1073/pnas.1120407109.
  • 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 GC, 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, Juppner 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, MJ van den Boogaard Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523. http://dx.doi.org/10.1016/S0092-8674(01)00571-2.
  • Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. 2002. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521. http://dx.doi.org/10.1056/NEJMoa013444.
  • 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. 2002. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 70:11–19. http://dx.doi.org/10.1086/338450.
  • Babij P, Zhao W, Small C, Kharode Y, Yaworsky PJ, Bouxsein ML, Reddy PS, Bodine PV, Robinson JA, Bhat B, Marzolf J, Moran RA, Bex F. 2003. High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 18:960–974. http://dx.doi.org/10.1359/jbmr.2003.18.6.960.
  • Shapiro I, Haselgrove J. 1991. Energy metabolism in bone, p 99–140. In Hall B (ed), Bone, vol 4: bone metabolism and mineralization. CRC Press, Boca Raton, FL.
  • Bolton JG, Patel S, Lacey JH, White S. 2005. A prospective study of changes in bone turnover and bone density associated with regaining weight in women with anorexia nervosa. Osteoporosis Int 16:1955–1962. http://dx.doi.org/10.1007/s00198-005-1972-7.
  • Nussbaum M, Baird D, Sonnenblick M, Cowan K, Shenker IR. 1985. Short stature in anorexia nervosa patients. J Adolesc Health Care 6:453–455. http://dx.doi.org/10.1016/S0197-0070(85)80052-8.
  • Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Aja S, Hussain MA, Bruning JC, Clemens TL. 2010. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142:309–319. http://dx.doi.org/10.1016/j.cell.2010.06.002.
  • Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P, Karsenty G. 2010. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308. http://dx.doi.org/10.1016/j.cell.2010.06.003.
  • Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G. 2007. Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469. http://dx.doi.org/10.1016/j.cell.2007.05.047.
  • Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G. 2011. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 50:568–575. http://dx.doi.org/10.1016/j.bone.2011.04.017.
  • Ferron M, Hinoi E, Karsenty G, Ducy P. 2008. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A 105:5266–5270. http://dx.doi.org/10.1073/pnas.0711119105.
  • Yoshikawa Y, Kode A, Xu L, Mosialou I, Silva BC, Ferron M, Clemens TL, Economides AN, Kousteni S. 2011. Genetic evidence points to an osteocalcin-independent influence of osteoblasts on energy metabolism. J Bone Miner Res 26:2012–2025. http://dx.doi.org/10.1002/jbmr.417.
  • Felix R, Neuman WF, Fleisch H. 1978. Aerobic glycolysis in bone: lactic acid production by rat calvaria cells in culture. Am J Physiol 234:C51–C55.
  • Schmid C, Steiner T, Froesch ER. 1982. Parathormone promotes glycogen formation from [14C]glucose in cultured osteoblast-like cells. FEBS Lett 148:31–34. http://dx.doi.org/10.1016/0014-5793(82)81236-2.
  • Schmid C, Steiner T, Froesch ER. 1983. Insulin-like growth factors stimulate synthesis of nucleic acids and glycogen in cultured calvaria cells. Calc Tissue Int 35:578–585. http://dx.doi.org/10.1007/BF02405097.
  • Adamek G, Felix R, Guenther HL, Fleisch H. 1987. Fatty acid oxidation in bone tissue and bone cells in culture: characterization and hormonal influences. Biochem J 248:129–137.
  • Niemeier A, Niedzielska D, Secer R, Schilling A, Merkel M, Enrich C, Rensen PC, Heeren J. 2008. Uptake of postprandial lipoproteins into bone in vivo: impact on osteoblast function. Bone 43:230–237. http://dx.doi.org/10.1016/j.bone.2008.03.022.
  • Bachner D, Schroder D, Betat N, Ahrens M, Gross G. 1999. Apolipoprotein E (ApoE), a Bmp-2 (bone morphogenetic protein) upregulated gene in mesenchymal progenitors (C3H10T1/2), is highly expressed in murine embryonic development. Biofactors 9:11–17. http://dx.doi.org/10.1002/biof.5520090103.
  • Catherwood BD, Addison J, Chapman G, Contreras S, Lorang M. 1988. Growth of rat osteoblast-like cells in a lipid-enriched culture medium and regulation of function by parathyroid hormone and 1,25-dihydroxyvitamin D. J Bone Miner Res 3:431–438.
  • Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, MacDougald OA. 2000. Inhibition of adipogenesis by Wnt signaling. Science 289:950–953. http://dx.doi.org/10.1126/science.289.5481.950.
  • Cawthorn WP, Bree AJ, Yao Y, Du B, Hemati N, Martinez-Santibanez G, MacDougald OA. 2012. Wnt6, Wnt10a, and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a beta-catenin-dependent mechanism. Bone 50:477–489. http://dx.doi.org/10.1016/j.bone.2011.08.010.
  • Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A, Styrkarsdottir U, Magnusson KP, Walters GB, Palsdottir E, Jonsdottir T, Gudmundsdottir T, Gylfason A, Saemundsdottir J, Wilensky RL, Reilly MP, Rader DJ, Bagger Y, Christiansen C, Gudnason V, Sigurdsson G, Thorsteinsdottir U, Gulcher JR, Kong A, Stefansson K. 2006. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320–323. http://dx.doi.org/10.1038/ng1732.
  • Tong Y, Lin Y, Zhang Y, Yang J, Zhang Y, Liu H, Zhang B. 2009. Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus: a large human genome epidemiology (HuGE) review and meta-analysis. BMC Med Genet 10:15. http://dx.doi.org/10.1186/1471-2350-10-15.
  • Guo YF, Xiong DH, Shen H, Zhao LJ, Xiao P, Guo Y, Wang W, Yang TL, Recker RR, Deng HW. 2006. 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 43:798–803. http://dx.doi.org/10.1136/jmg.2006.041715.
  • Go GW, Srivastava R, Hernandez-Ono A, Gang G, Smith SB, Booth CJ, Ginsberg HN, Mani A. 2014. The combined hyperlipidemia caused by impaired Wnt-LRP6 signaling is reversed by Wnt3a rescue. Cell Metab 19:209–220. http://dx.doi.org/10.1016/j.cmet.2013.11.023.
  • Huertas-Vazquez A, Plaisier C, Weissglas-Volkov D, Sinsheimer J, Canizales-Quinteros S, Cruz-Bautista I, Nikkola E, Herrera-Hernandez M, Davila-Cervantes A, Tusie-Luna T, Taskinen MR, Aguilar-Salinas C, Pajukanta P. 2008. TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia. Diabetologia 51:62–69.
  • Hey PJ, Twells RC, Phillips MS, Yusuke N, Brown SD, Kawaguchi Y, Cox R, Guochun X, Dugan V, Hammond H, Metzker ML, Todd JA, Hess JF. 1998. Cloning of a novel member of the low-density lipoprotein receptor family. Gene 216:103–111. http://dx.doi.org/10.1016/S0378-1119(98)00311-4.
  • Twells RC, Metzker ML, Brown SD, Cox R, Garey C, Hammond H, Hey PJ, Levy E, Nakagawa Y, Philips MS, Todd JA, Hess JF. 2001. The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13. Genomics 72:231–242. http://dx.doi.org/10.1006/geno.2000.6492.
  • Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, Takada S, Kim DH, Ioka RX, Ono M, Tomoyori H, Okubo M, Murase T, Kamataki A, Yamamoto J, Magoori K, Takahashi S, Miyamoto Y, Oishi H, Nose M, Okazaki M, Usui S, Imaizumi K, Yanagisawa M, Sakai J, Yamamoto TT. 2003. 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 100:229–234. http://dx.doi.org/10.1073/pnas.0133792100.
  • Magoori K, Kang MJ, Ito MR, Kakuuchi H, Ioka RX, Kamataki A, Kim DH, Asaba H, Iwasaki S, Takei YA, Sasaki M, Usui S, Okazaki M, Takahashi S, Ono M, Nose M, Sakai J, Fujino T, Yamamoto TT. 2003. Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E. J Biol Chem 278:11331–11336. http://dx.doi.org/10.1074/jbc.M211987200.
  • Zhang M, Xuan S, Bouxsein ML, von Stechow D, Akeno N, Faugere MC, Malluche H, Zhao G, Rosen CJ, Efstratiadis A, Clemens TL. 2002. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem 277:44005–44012. http://dx.doi.org/10.1074/jbc.M208265200.
  • Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schutz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G. 2008. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135:825–837. http://dx.doi.org/10.1016/j.cell.2008.09.059.
  • Lin SM, Du P, Huber W, Kibbe WA. 2008. Model-based variance-stabilizing transformation for Illumina microarray data. Nucleic Acids Res 36:e11. http://dx.doi.org/10.1093/nar/gkm1075.
  • Du P, Kibbe WA, Lin SM. 2008. Lumi: a pipeline for processing Illumina microarray. Bioinformatics 24:1547–1548. http://dx.doi.org/10.1093/bioinformatics/btn224.
  • Smyth GK. 2004. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:Article3.
  • Ellis JM, Wong GW, Wolfgang MJ. 2013. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity. Mol Cell Biol 33:1869–1882. http://dx.doi.org/10.1128/MCB.01548-12.
  • Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R. 2010. Guidelines for assessment of bone microstructure in rodents using microcomputed tomography. J Bone Miner Res 25:1468–1486. http://dx.doi.org/10.1002/jbmr.141.
  • Lusk G. 1928. The elements of the science of nutrition. WB Saunders, Philadelphia, PA.
  • Xiao F, Huang Z, Li H, Yu J, Wang C, Chen S, Meng Q, Cheng Y, Gao X, Li J, Liu Y, Guo F. 2011. Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways. Diabetes 60:746–756. http://dx.doi.org/10.2337/db10-1246.
  • Zhang Q, Yu J, Liu B, Lv Z, Xia T, Xiao F, Chen S, Guo F. 2013. Central activating transcription factor 4 (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve. Diabetes 62:2230–2239. http://dx.doi.org/10.2337/db12-1050.
  • Hussain MA, Porras DL, Rowe MH, West JR, Song WJ, Schreiber WE, Wondisford FE. 2006. Increased pancreatic beta-cell proliferation mediated by CREB binding protein gene activation. Mol Cell Biol 26:7747–7759. http://dx.doi.org/10.1128/MCB.02353-05.
  • Palsgaard J, Emanuelli B, Winnay JN, Sumara G, Karsenty G, Kahn CR. 2012. Cross-talk between insulin and Wnt signaling in preadipocytes: role of Wnt coreceptor low density lipoprotein receptor-related protein-5 (LRP5). J Biol Chem 287:12016–12026. http://dx.doi.org/10.1074/jbc.M111.337048.
  • Clemens TL, Karsenty G. 2011. The osteoblast: an insulin target cell controlling glucose homeostasis. J Bone Miner Res 26:677–680. http://dx.doi.org/10.1002/jbmr.321.
  • Weis BC, Cowan AT, Brown N, Foster DW, McGarry JD. 1994. Use of a selective inhibitor of liver carnitine palmitoyltransferase I (CPT I) allows quantification of its contribution to total CPT I activity in rat heart. Evidence that the dominant cardiac CPT I isoform is identical to the skeletal muscle enzyme. J Biol Chem 269:26443–26448.
  • Esen E, Chen J, Karner CM, Okunade AL, Patterson BW, Long F. 2013. WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. Cell Metab 17:745–755. http://dx.doi.org/10.1016/j.cmet.2013.03.017.
  • Hedgepeth CM, Conrad LJ, Zhang J, Huang HC, Lee VM, Klein PS. 1997. Activation of the Wnt signaling pathway: a molecular mechanism for lithium action. Dev Biol 185:82–91. http://dx.doi.org/10.1006/dbio.1997.8552.
  • Karsenty G, Oury F. 2012. Biology without walls: the novel endocrinology of bone. Annu Rev Physiol 74:87–105. http://dx.doi.org/10.1146/annurev-physiol-020911-153233.
  • Karsenty G, Ferron M. 2012. The contribution of bone to whole-organism physiology. Nature 481:314–320. http://dx.doi.org/10.1038/nature10763.
  • DiGirolamo DJ, Clemens TL, Kousteni S. 2012. The skeleton as an endocrine organ. Nat Rev Rheumatol 8:674–683. http://dx.doi.org/10.1038/nrrheum.2012.157.
  • Suwazono Y, Kobayashi E, Uetani M, Miura K, Morikawa Y, Ishizaki M, Kido T, Nakagawa H, Nogawa K. 2006. G-protein beta 3 subunit polymorphism C1429T and low-density lipoprotein receptor-related protein 5 polymorphism A1330V are risk factors for hypercholesterolemia in Japanese males: a prospective study over 5 years. Metab Clin Exp 55:751–757. http://dx.doi.org/10.1016/j.metabol.2006.01.011.
  • Suwazono Y, Kobayashi E, Uetani M, Miura K, Morikawa Y, Ishizaki M, Kido T, Nakagawa H, Nogawa K. 2006. Low-density lipoprotein receptor-related protein 5 variant Q89R is associated with hypertension in Japanese females. Blood Pressure 15:80–87. http://dx.doi.org/10.1080/08037050600650191.
  • Lappalainen S, Saarinen A, Utriainen P, Voutilainen R, Jaaskelainen J, Makitie O. 2009. LRP5 in premature adrenarche and in metabolic characteristics of prepubertal children. Clin Endocrinol 70:725–731. http://dx.doi.org/10.1111/j.1365-2265.2008.03388.x.
  • Song L, Liu M, Ono N, Bringhurst FR, Kronenberg HM, Guo J. 2012. Loss of wnt/beta-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes. J Bone Miner Res 27:2344–2358. http://dx.doi.org/10.1002/jbmr.1694.
  • 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. 2011. Lrp5 functions in bone to regulate bone mass. Nat Med 17:684–691. http://dx.doi.org/10.1038/nm.2388.
  • Boj SF, van Es JH, Huch M, Li VS, Jose A, Hatzis P, Mokry M, Haegebarth A, van den Born M, Chambon P, Voshol P, Dor Y, Cuppen E, Fillat C, Clevers H. 2012. Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand. Cell 151:1595–1607. http://dx.doi.org/10.1016/j.cell.2012.10.053.
  • He X, Semenov M, Tamai K, Zeng X. 2004. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development 131:1663–1677. http://dx.doi.org/10.1242/dev.01117.
  • Brown SD, Twells RC, Hey PJ, Cox RD, Levy ER, Soderman AR, Metzker ML, Caskey CT, Todd JA, Hess JF. 1998. Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. Biochem Biophys Res Commun 248:879–888. http://dx.doi.org/10.1006/bbrc.1998.9061.
  • Chen D, Lathrop W, Dong Y. 1999. Molecular cloning of mouse Lrp7(Lr3) cDNA and chromosomal mapping of orthologous genes in mouse and human. Genomics 55:314–321. http://dx.doi.org/10.1006/geno.1998.5688.
  • Holmen SL, Salic A, Zylstra CR, Kirschner MW, Williams BO. 2002. A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta-catenin-dependent signaling. J Biol Chem 277:34727–34735. http://dx.doi.org/10.1074/jbc.M204989200.
  • Kelly OG, Pinson KI, Skarnes WC. 2004. The Wnt coreceptors Lrp5 and Lrp6 are essential for gastrulation in mice. Development 131:2803–2815. http://dx.doi.org/10.1242/dev.01137.
  • Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X. 2000. LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530–535. http://dx.doi.org/10.1038/35035117.
  • MacDonald BT, Semenov MV, Huang H, He X. 2011. Dissecting molecular differences between Wnt coreceptors LRP5 and LRP6. PLoS One 6:e23537. http://dx.doi.org/10.1371/journal.pone.0023537.
  • Kim DH, Inagaki Y, Suzuki T, Ioka RX, Yoshioka SZ, Magoori K, Kang MJ, Cho Y, Nakano AZ, Liu Q, Fujino T, Suzuki H, Sasano H, Yamamoto TT. 1998. A new low density lipoprotein receptor related protein, LRP5, is expressed in hepatocytes and adrenal cortex, and recognizes apolipoprotein E. J Biochem 124:1072–1076. http://dx.doi.org/10.1093/oxfordjournals.jbchem.a022223.
  • Liu W, Mani S, Davis NR, Sarrafzadegan N, Kavathas PB, Mani A. 2008. Mutation in EGFP domain of LDL receptor-related protein 6 impairs cellular LDL clearance. Circ Res 103:1280–1288. http://dx.doi.org/10.1161/CIRCRESAHA.108.183863.
  • Ye ZJ, Go GW, Singh R, Liu W, Keramati AR, Mani A. 2012. LRP6 protein regulates low density lipoprotein (LDL) receptor-mediated LDL uptake. J Biol Chem 287:1335–1344. http://dx.doi.org/10.1074/jbc.M111.295287.
  • Mani A, Radhakrishnan J, Wang H, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP. 2007. LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315:1278–1282. http://dx.doi.org/10.1126/science.1136370.
  • Joeng KS, Schumacher CA, Zylstra-Diegel CR, Long F, Williams BO. 2011. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev Biol 359:222–229. http://dx.doi.org/10.1016/j.ydbio.2011.08.020.
  • Samuel VT, Shulman GI. 2012. Mechanisms for insulin resistance: common threads and missing links. Cell 148:852–871. http://dx.doi.org/10.1016/j.cell.2012.02.017.
  • Semenov M, Tamai K, He X. 2005. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280:26770–26775. http://dx.doi.org/10.1074/jbc.M504308200.
  • Urano T, Shiraki M, Ouchi Y, Inoue S. 2012. Association of circulating sclerostin levels with fat mass and metabolic disease-related markers in Japanese postmenopausal women. The J clinical endocrinology and metabolism 97:E1473–E1477. http://dx.doi.org/10.1210/jc.2012-1218.
  • Garcia-Martin A, Rozas-Moreno P, Reyes-Garcia R, Morales-Santana S, Garcia-Fontana B, Garcia-Salcedo JA, Munoz-Torres M. 2012. Circulating levels of sclerostin are increased in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 97:234–241. http://dx.doi.org/10.1210/jc.2011-2186.
  • Amrein K, Amrein S, Drexler C, Dimai HP, Dobnig H, Pfeifer K, Tomaschitz A, Pieber TR, Fahrleitner-Pammer A. 2012. Sclerostin and its association with physical activity, age, gender, body composition, and bone mineral content in healthy adults. J Clin Endocrinol Metab 97:148–154. http://dx.doi.org/10.1210/jc.2011-2152.
  • Ominsky MS, Li C, Li X, Tan HL, Lee E, Barrero M, Asuncion FJ, Dwyer D, Han CY, Vlasseros F, Samadfam R, Jolette J, Smith SY, Stolina M, Lacey DL, Simonet WS, Paszty C, Li G, Ke HZ. 2011. Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones. J Bone Miner Res 26:1012–1021. http://dx.doi.org/10.1002/jbmr.307.
  • Tian X, Jee WS, Li X, Paszty C, Ke HZ. 2011. Sclerostin antibody increases bone mass by stimulating bone formation and inhibiting bone resorption in a hindlimb-immobilization rat model. Bone 48:197–201. http://dx.doi.org/10.1016/j.bone.2010.09.009.

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