Osteoblastogenesis regulation signals in bone remodeling

Osteoporosis International

Volumn 23, Issue 6, 2012, Pages 1653-1663

  Zuo, C ^a   Huang, Y ^b   Bajis, R ^c   Sahih, M ^c   Li, Y P ^d   Dai, K ^a,b   Zhang, X ^a,b  

^a SHANGHAI JIAO TONG UNIVERSITY   (China)

^b SHANGHAI SECOND MEDICAL UNIVERSITY   (China)

^c UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^d University of Alabama at Birmingham   (United States)

Author keywords

Bone remodeling; Osteoblastogenesis; Signals

Indexed keywords

BONE MORPHOGENETIC PROTEIN; EPHRIN; LEPTIN; NOTCH RECEPTOR; PARATHYROID HORMONE; PARATHYROID HORMONE RELATED PROTEIN; SEROTONIN; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEIN;

ADRENERGIC SYSTEM; BONE METABOLISM; BONE REMODELING; CELL GROWTH; HUMAN; NONHUMAN; OSSIFICATION; OSTEOBLAST; OSTEOBLASTOGENESIS; OSTEOPOROSIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW;

ANIMALS; BONE MORPHOGENETIC PROTEINS; BONE REMODELING; CELL COMMUNICATION; EPHRINS; HUMANS; LEPTIN; OSTEOBLASTS; PARATHYROID HORMONE; PARATHYROID HORMONE-RELATED PROTEIN; SEROTONIN; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA; WNT SIGNALING PATHWAY;

EID: 84863633404     PISSN: 0937941X     EISSN: 14332965     Source Type: Journal    
DOI: 10.1007/s00198-012-1909-x     Document Type: Review

References (103)

1. Harvey N, Dennison E, Cooper C (2010) Osteoporosis: impact on health and economics. Nat Rev Rheumatol 6:99-105.
2. Canalis E, Giustina A, Bilezikian JP (2007) Mechanisms of anabolic therapies for osteoporosis. N Engl J Med 357:905-916.
3. Khosla S, Westendorf JJ, Oursler MJ (2008) Building bone to reverse osteoporosis and repair fractures. J Clin Invest 118:421-428. (Pubitemid 351206529)
4. Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F (2001) Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res 16:1575-1582. (Pubitemid 32786425)
5. Chambers TJ, Fuller K (1985) Bone cells predispose bone surfaces to resorption by exposure of mineral to osteoclastic contact. J Cell Sci 76:155-165. (Pubitemid 16246175)
6. Everts V, Delaisse JM, Korper W, Jansen DC, Tigchelaar-Gutter W, Saftig P, Beertsen W (2002) The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation. J Bone Miner Res 17:77-90. (Pubitemid 33150999)
7. Hadjidakis DJ, Androulakis II (2006) Bone remodeling. Ann N Y Acad Sci 1092:385-396. (Pubitemid 47092355)
8. Janssens K, ten Dijke P, Janssens S, Van Hul W (2005) Transforming growth factor-beta1 to the bone. Endocr Rev 26:743-774.
9. Cao X, Chen D (2005) The BMP signaling and in vivo bone formation. Gene 357:1-8. (Pubitemid 41267309)
10. Geiser AG, Zeng QQ, Sato M, Helvering LM, Hirano T, Turner CH (1998) Decreased bone mass and bone elasticity in mice lacking the transforming growth factor-beta1 gene. Bone 23:87-93. (Pubitemid 28379868)
11. Atti E, Gomez S, Wahl SM, Mendelsohn R, Paschalis E, Boskey AL (2002) Effects of transforming growth factor-beta deficiency on bone development: a Fourier transform-infrared imaging analysis. Bone 31:675-684. (Pubitemid 36092090)
12. Sanford LP, Ormsby I, Gittenberger-de Groot AC, Sariola H, Friedman R, Boivin GP, Cardell EL, Doetschman T (1997) TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development 124:2659-2670. (Pubitemid 27341765)
13. Proetzel G, Pawlowski SA, Wiles MV, Yin M, Boivin GP, Howles PN, Ding J, Ferguson MW, Doetschman T (1995) Transforming growth factor-beta 3 is required for secondary palate fusion. Nat Genet 11:409-414. (Pubitemid 3007193)
14. Borton AJ, Frederick JP, Datto MB, Wang XF, Weinstein RS (2001) The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res 16:1754-1764. (Pubitemid 32911480)
15. Hock JM, Canalis E, Centrella M (1990) Transforming growth factor-beta stimulates bone matrix apposition and bone cell replication in cultured fetal rat calvariae. Endocrinology 126:421-426. (Pubitemid 20037172)
16. Maeda S, Hayashi M, Komiya S, Imamura T, Miyazono K (2004) Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J 23:552-563. (Pubitemid 38282387)
17. Seitz PK, Zhu BT, Cooper CW (1992) Effect of transforming growth factor beta on parathyroid hormone receptor binding and cAMP formation in rat osteosarcoma cells. J Bone Miner Res 7:541-546.
18. Wu Y, Kumar R (2000) Parathyroid hormone regulates transforming growth factor beta1 and beta2 synthesis in osteoblasts via divergent signaling pathways. J Bone Miner Res 15:879-884. (Pubitemid 30233411)
19. Qiu T,Wu X, Zhang F, Clemens TL,Wan M, Cao X (2010) TGFbeta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling. Nat Cell Biol 12:224-234.
20. Pelton RW, Saxena B, Jones M, Moses HL, Gold LI (1991) Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J Cell Biol 115:1091-1105. (Pubitemid 21909956)
21. Pfeilschifter J, Mundy GR (1987) Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones. Proc Natl Acad Sci USA 84:2024-2028. (Pubitemid 17054142)
22. Erlebacher A, Derynck R (1996) Increased expression of TGFbeta 2 in osteoblasts results in an osteoporosis-like phenotype. J Cell Biol 132:195-210.
23. Erlebacher A, Filvaroff EH, Ye JQ, Derynck R (1998) Osteoblastic responses to TGF-beta during bone remodeling. Mol Biol Cell 9:1903-1918. (Pubitemid 28337531)
24. Tang Y, Wu X, Lei Wet al (2009) TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med 15:757-765.
25. Urist MR (1965) Bone: formation by autoinduction. Science 150:893-899.
26. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA (1988) Novel regulators of bone formation: molecular clones and activities. Science 242:1528-1534. (Pubitemid 19023695)
27. Bandyopadhyay A, Tsuji K, Cox K, Harfe BD, Rosen V, Tabin CJ (2006) Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet 2:e216.
28. Zhao M, Harris SE, Horn D, Geng Z, Nishimura R, Mundy GR, Chen D (2002) Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. J Cell Biol 157:1049-1060. (Pubitemid 34839779)
29. Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22:233-241. (Pubitemid 40136452)
30. Canalis E, Economides AN, Gazzerro E (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 24:218-235. (Pubitemid 36515285)
31. Devlin RD, Du Z, Pereira RC, Kimble RB, Economides AN, Jorgetti V, Canalis E (2003) Skeletal overexpression of noggin results in osteopenia and reduced bone formation. Endocrinology 144:1972-1978. (Pubitemid 36543336)
32. Gazzerro E, Pereira RC, Jorgetti V, Olson S, Economides AN, Canalis E (2005) Skeletal overexpression of gremlin impairs bone formation and causes osteopenia. Endocrinology 146:655-665. (Pubitemid 40129821)
33. Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202-1209.
34. Gong Y, Slee RB, Fukai N et al (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513-523. (Pubitemid 33152786)
35. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A,MitnickMA,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. (Pubitemid 34755690)
36. Kato M, Patel MS, Levasseur R et al (2002) Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 157:303-314. (Pubitemid 34839826)
37. Babij P, Zhao W, Small C et al (2003) High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 18:960-974. (Pubitemid 37294932)
38. Holmen SL, Giambernardi TA, Zylstra CR et al (2004) Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res 19:2033-2040. (Pubitemid 41103418)
39. Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739-750. (Pubitemid 40585296)
40. 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. (Pubitemid 40585295)
41. Bennett CN, Longo KA,WrightWS, Suva LJ, Lane TF, Hankenson KD, MacDougald OA (2005) Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA 102:3324-3329. (Pubitemid 40328044)
42. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132:49-60. (Pubitemid 40207966)
43. Stambolic V, Ruel L, Woodgett JR (1996) Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol 6:1664-1668. (Pubitemid 27050234)
44. Clement-Lacroix P, Ai M, Morvan F, Roman-Roman S, Vayssiere B, Belleville C, Estrera K, Warman ML, Baron R, Rawadi G (2005) Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci USA 102:17406-17411. (Pubitemid 41740879)
45. Glass DA 2nd, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751-764. (Pubitemid 40585297)
46. Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627-2634. (Pubitemid 36857216)
47. Li X, Ominsky MS, Niu QT et al (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23:860-869. (Pubitemid 351768804)
48. Li X, Ominsky MS, Warmington KS et al (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24:578-588.
49. Bodine PV, Zhao W, Kharode YP, Bex FJ, Lambert AJ, Goad MB, Gaur T, Stein GS, Lian JB, Komm BS (2004) The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol Endocrinol 18:1222-1237. (Pubitemid 38591287)
50. Bodine PV, Stauffer B, Ponce-de-Leon H et al (2009) A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation. Bone 44:1063-1068.
51. Morvan F, Boulukos K, Clement-Lacroix P et al (2006) Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21:934-945. (Pubitemid 43788000)
52. Glantschnig H, Hampton RA, Lu P et al (2010) Generation and selection of novel fully human monoclonal antibodies that neutralize Dickkopf-1 (DKK1) inhibitory function in vitro and increase bone mass in vivo. J Biol Chem 285:40135-40147.
53. Canalis E (2008) Notch signaling in osteoblasts. Sci Signal 1: pe17.
54. Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, Tonegawa S (1997) Skeletal and CNS defects in Presenilin-1-deficient mice. Cell 89:629-639. (Pubitemid 27511773)
55. Li L, Krantz ID, Deng Yet al (1997) Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet 16:243-251.
56. Oda T, Elkahloun AG, Pike BL et al (1997) Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet 16:235-242.
57. Bulman MP, Kusumi K, Frayling TM, McKeown C, Garrett C, Lander ES, Krumlauf R, Hattersley AT, Ellard S, Turnpenny PD (2000) Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis. Nat Genet 24:438-441. (Pubitemid 30187449)
58. Engin F, Yao Z, Yang T et al (2008) Dimorphic effects of Notch signaling in bone homeostasis. Nat Med 14:299-305. (Pubitemid 351347909)
59. Hilton MJ, Tu X, Wu X et al (2008) Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med 14:306-314. (Pubitemid 351347911)
60. Matsuo K (2010) Eph and ephrin interactions in bone. Adv Exp Med Biol 658:95-103.
61. Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K (2006) Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab 4:111-121. (Pubitemid 44138718)
62. Allan EH, Hausler KD, Wei T et al (2008) EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblasts. J Bone Miner Res 23:1170-1181. (Pubitemid 352040173)
63. Xing W, Kim J, Wergedal J, Chen ST, Mohan S (2010) Ephrin B1 regulates bone marrow stromal cell differentiation and bone formation by influencing TAZ transactivation via complex formation with NHERF1. Mol Cell Biol 30:711-721.
64. Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, Matsuo K (2009) Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J Biol Chem 284:14637-14644.
65. Goltzman D (2008) Studies on the mechanisms of the skeletal anabolic action of endogenous and exogenous parathyroid hormone. Arch Biochem Biophys 473:218-224.
66. Neer RM, Arnaud CD, Zanchetta JR et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434-1441. (Pubitemid 32402100)
67. Chen P, Miller PD, Delmas PD, Misurski DA, Krege JH (2006) Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res 21:1785-1790. (Pubitemid 46141234)
68. Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ (2003) The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med 349:1207-1215. (Pubitemid 37152030)
69. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, McGowan JA, Rosen CJ (2005) One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med 353:555-565. (Pubitemid 41138937)
70. Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB (2007) Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res 22:495-502. (Pubitemid 47457425)
71. Stewart AF, Cain RL, Burr DB, Jacob D, Turner CH, Hock JM (2000) Six-month daily administration of parathyroid hormone and parathyroid hormone-related protein peptides to adult ovariectomized rats markedly enhances bone mass and biomechanical properties: a comparison of human parathyroid hormone 1-34, parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893. J Bone Miner Res 15:1517-1525. (Pubitemid 30484521)
72. Horwitz MJ, Tedesco MB, Gundberg C, Garcia-Ocana A, Stewart AF (2003) Short-term, high-dose parathyroid hormone-related protein as a skeletal anabolic agent for the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab 88:569-575. (Pubitemid 36207792)
73. Miao D, He B, Karaplis AC, Goltzman D (2002) Parathyroid hormone is essential for normal fetal bone formation. J Clin Invest 109:1173-1182. (Pubitemid 34496595)
74. Amizuka N, Karaplis AC, Henderson JE et al (1996) Haploinsufficiency of parathyroid hormone-related peptide (PTHrP) results in abnormal postnatal bone development. Dev Biol 175:166-176. (Pubitemid 26148780)
75. Miao D, He B, Jiang Yet al (2005) Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34. J Clin Invest 115:2402-2411. (Pubitemid 41266202)
76. Lanske B, Amling M, Neff L, Guiducci J, Baron R, Kronenberg HM (1999) Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development. J Clin Invest 104:399-407. (Pubitemid 29534324)
77. Calvi LM, Sims NA, Hunzelman JL, Knight MC, Giovannetti A, Saxton JM, Kronenberg HM, Baron R, Schipani E (2001) Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone. J Clin Invest 107:277-286. (Pubitemid 32157960)
78. Datta NS, Abou-Samra AB (2009) PTH and PTHrP signaling in osteoblasts. Cell Signal 21:1245-1254.
79. Juppner H, Abou-Samra AB, Freeman M et al (1991) A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 254:1024-1026. (Pubitemid 21917436)
80. Nishida S, Yamaguchi A, Tanizawa T, Endo N, Mashiba T, Uchiyama Y, Suda T, Yoshiki S, Takahashi HE (1994) Increased bone formation by intermittent parathyroid hormone administration is due to the stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow. Bone 15:717-723. (Pubitemid 24332666)
81. Datta NS, Pettway GJ, Chen C, Koh AJ, McCauley LK (2007) Cyclin D1 as a target for the proliferative effects of PTH and PTHrP in early osteoblastic cells. J Bone Miner Res 22:951-964. (Pubitemid 351339717)
82. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC (1999) Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104:439-446. (Pubitemid 29534328)
83. Dobnig H, Turner RT (1995) Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136:3632-3638.
84. Canalis E, Centrella M, Burch W, McCarthy TL (1989) Insulinlike growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 83:60-65. (Pubitemid 19048405)
85. Bikle DD, Sakata T, Leary C, Elalieh H, Ginzinger D, Rosen CJ, Beamer W, Majumdar S, Halloran BP (2002) Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone. J Bone Miner Res 17:1570-1578.
86. Wang Y, Nishida S, Boudignon BM, Burghardt A, Elalieh HZ, Hamilton MM, Majumdar S, Halloran BP, Clemens TL, Bikle DD (2007) IGF-I receptor is required for the anabolic actions of parathyroid hormone on bone. J Bone Miner Res 22:1329-1337. (Pubitemid 351339678)
87. Keller H, Kneissel M (2005) SOST is a target gene for PTH in bone. Bone 37:148-158. (Pubitemid 40962421)
88. Kramer I, Loots GG, Studer A, Keller H, Kneissel M (2010) Parathyroid hormone (PTH)-induced bone gain is blunted in SOST overexpressing and deficient mice. J Bone Miner Res 25:178-189.
89. Dempster DW, Hughes-Begos CE, Plavetic-Chee K et al (2005) Normal human osteoclasts formed from peripheral blood monocytes express PTH type 1 receptors and are stimulated by PTH in the absence of osteoblasts. J Cell Biochem 95:139-148. (Pubitemid 41420224)
90. Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552-3561. (Pubitemid 30645409)
91. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197-207. (Pubitemid 30064908)
92. Elefteriou F, Takeda S, Ebihara K et al (2004) Serum leptin level is a regulator of bone mass. Proc Natl Acad Sci USA 101:3258-3263. (Pubitemid 38327768)
93. Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL (1999) Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 140:1630-1638. (Pubitemid 29149231)
94. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305-317. (Pubitemid 35345151)
95. Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G (2005) The molecular clock mediates leptin-regulated bone formation. Cell 122:803-815. (Pubitemid 41242643)
96. Elefteriou F, Ahn JD, Takeda S et al (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514-520. (Pubitemid 40477060)
97. Rejnmark L, Vestergaard P, Kassem M, Christoffersen BR, Kolthoff N, Brixen K, Mosekilde L (2004) Fracture risk in perimenopausal women treated with beta-blockers. Calcif Tissue Int 75:365-372. (Pubitemid 40100883)
98. Reid IR, Gamble GD, Grey AB, Black DM, Ensrud KE, Browner WS, Bauer DC (2005) beta-Blocker use, BMD, and fractures in the study of osteoporotic fractures. J Bone Miner Res 20:613-618. (Pubitemid 40393069)
99. Balthasar N, Coppari R, McMinn J et al (2004) Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42:983-991. (Pubitemid 38798236)
100. Yadav VK, Oury F, Suda N et al (2009) A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138:976-989
101. Yadav VK, Ryu JH, Suda N et al (2008) Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135:825-837
102. Yadav VK, Balaji S, Suresh PS et al (2010) Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med 16:308-312
103. Cui Y, Niziolek PJ, MacDonald BT et al (2011) Lrp5 functions in bone to regulate bone mass. Nat Med 17:684-691