Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models

Growth Hormone and IGF Research

Volumn 28, Issue , 2016, Pages 26-42

  Yakar, Shoshana ^a   Isaksson, Olle ^b  

^a NEW YORK UNIVERSITY COLLEGE OF DENTISTRY   (United States)

^b SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Chondrocyte; Endosteum; Growth hormone (GH); Growth hormone receptor (GHR); Growth plate; Histomorphometry; Insulin like growth factor 1 (IGF 1); Mechanical stimuli; Micro CT; Mineralization; Osteoblast; Osteocyte; Perichondrium; Periosteum

Indexed keywords

GROWTH HORMONE; GROWTH HORMONE RECEPTOR; METALLOTHIONEIN I; PARATHYROID HORMONE; SEX HORMONE; SOMATOMEDIN B; SOMATOMEDIN BINDING PROTEIN; SOMATOMEDIN C; SOMATOMEDIN C RECEPTOR; THYROID HORMONE; INSULIN-LIKE GROWTH FACTOR-1, MOUSE;

AGING; ARTICLE; BODY SIZE; BONE DENSITY; BONE GROWTH; BONE METABOLISM; BONE MINERALIZATION; BONE REMODELING; BONE STRESS; CELL CULTURE; CELL DIFFERENTIATION; CELL FUNCTION; GROWTH HORMONE BLOOD LEVEL; GROWTH PLATE; HORMONAL REGULATION; HORMONE ACTION; MECHANICAL STRESS; METABOLISM; MOUSE; MOUSE MODEL; NONHUMAN; OSTEOBLAST; OSTEOCYTE; OSTEOLYSIS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; ANIMAL; BONE; BONE DEVELOPMENT;

ANIMALS; BONE AND BONES; BONE DEVELOPMENT; CALCIFICATION, PHYSIOLOGIC; GROWTH HORMONE; INSULIN-LIKE GROWTH FACTOR I; MICE; OSTEOGENESIS;

EID: 84945549292     PISSN: 10966374     EISSN: 15322238     Source Type: Journal    
DOI: 10.1016/j.ghir.2015.09.004     Document Type: Article

References (175)

1. Goldenberg N., Barkan A. Factors regulating growth hormone secretion in humans. Endocrinol. Metab. Clin. N. Am. 2007, 36:37-55.
2. Waters M.J., Brooks A.J. Growth hormone receptor: structure function relationships. Horm. Res. Paediatr. 2011, 76(Suppl. 1):12-16.
3. Brown R.J., Adams J.J., Pelekanos R.A., Wan Y., McKinstry W.J., Palethorpe K., Seeber R.M., Monks T.A., Eidne K.A., Parker M.W., Waters M.J. Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat. Struct. Mol. Biol. 2005, 12:814-821.
4. Hilton D.J. Negative regulators of cytokine signal transduction. Cell. Mol. Life Sci. 1999, 55:1568-1577.
5. Zhang J.G., Farley A., Nicholson S.E., Willson T.A., Zugaro L.M., Simpson R.J., Moritz R.L., Cary D., Richardson R., Hausmann G., Kile B.T., Kent S.B., Alexander W.S., Metcalf D., Hilton D.J., Nicola N.A., Baca M. The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:2071-2076.
6. Mayo K.E., Hammer R.E., Swanson L.W., Brinster R.L., Rosenfeld M.G., Evans R.M. Dramatic pituitary hyperplasia in transgenic mice expressing a human growth hormone-releasing factor gene. Mol. Endocrinol. 1988, 2:606-612.
7. Hammer R.E., Brinster R.L., Rosenfeld M.G., Evans R.M., Mayo K.E. Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth. Nature 1985, 315:413-416.
8. Steinke B., Patwardhan A.G., Havey R.M., King D. Human growth hormone transgene expression increases the biomechanical structural properties of mouse vertebrae. Spine (Phila Pa 1976) 1999, 24:1-4.
9. Tseng K.F., Bonadio J.F., Stewart T.A., Baker A.R., Goldstein S.A. Local expression of human growth hormone in bone results in impaired mechanical integrity in the skeletal tissue of transgenic mice. J. Orthop. Res. 1996, 14:598-604.
10. Wanke R., Wolf E., Hermanns W., Folger S., Buchmuller T., Brem G. The GH-transgenic mouse as an experimental model for growth research: clinical and pathological studies. Horm. Res. 1992, 37(Suppl. 3):74-87.
11. Wanke R., Hermanns W., Folger S., Wolf E., Brem G. Accelerated growth and visceral lesions in transgenic mice expressing foreign genes of the growth hormone family: an overview. Pediatr. Nephrol. 1991, 5:513-521.
12. Wolf E., Rapp K., Brem G. Expression of metallothionein-human growth hormone fusion genes in transgenic mice results in disproportionate skeletal gigantism. Growth Dev. Aging 1991, 55:117-127.
13. Wolf E., Rapp K., Wanke R., Hermanns W., Pirchner F., von Butler-Wemken I., Brem G. Growth characteristics of metallothionein-human growth hormone transgenic mice as compared to mice selected for high eight-week body weight and unselected controls. II. Skeleton. Growth Dev. Aging 1991, 55:237-248.
14. Wolf E., Wanke R., Hermanns W., Brem G., Pirchner F., von Butler-Wemken I. Growth characteristics of metallothionein-human growth hormone transgenic mice as compared to mice selected for high eight-week body weight and unselected controls. I. Body weight gain and external body dimensions. Growth Dev. Aging 1991, 55:225-235.
15. Lim S.V., Marenzana M., Hopkinson M., List E.O., Kopchick J.J., Pereira M., Javaheri B., Roux J.P., Chavassieux P., Korbonits M., Chenu C. Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength. Endocrinology 2015, 156:1362-1371.
16. Palmer A.J., Chung M.Y., List E.O., Walker J., Okada S., Kopchick J.J., Berryman D.E. Age-related changes in body composition of bovine growth hormone transgenic mice. Endocrinology 2009, 150:1353-1360.
17. Eckstein F., Weusten A., Schmidt C., Wehr U., Wanke R., Rambeck W., Wolf E., Mohan S. Longitudinal in vivo effects of growth hormone overexpression on bone in transgenic mice. J. Bone Miner. Res. 2004, 19:802-810.
18. Bartke A., Chandrashekar V., Bailey B., Zaczek D., Turyn D. Consequences of growth hormone (GH) overexpression and GH resistance. Neuropeptides 2002, 36:201-208.
19. Eckstein F., Lochmuller E.M., Koller B., Wehr U., Weusten A., Rambeck W., Hoeflich A., Wolf E. Body composition, bone mass and microstructural analysis in GH-transgenic mice reveals that skeletal changes are specific to bone compartment and gender. Growth Hormon. IGF Res. 2002, 12:116-125.
20. Tseng K.F., Goldstein S.A. Systemic over-secretion of growth hormone in transgenic mice results in a specific pattern of skeletal modeling and adaptation. J. Bone Miner. Res. 1998, 13:706-715.
21. Sandstedt J., Tornell J., Norjavaara E., Isaksson O.G., Ohlsson C. Elevated levels of growth hormone increase bone mineral content in normal young mice, but not in ovariectomized mice. Endocrinology 1996, 137:3368-3374.
22. Metcalf D., Greenhalgh C.J., Viney E., Willson T.A., Starr R., Nicola N.A., Hilton D.J., Alexander W.S. Gigantism in mice lacking suppressor of cytokine signalling-2. Nature 2000, 405:1069-1073.
23. Macrae V.E., Horvat S., Pells S.C., Dale H., Collinson R.S., Pitsillides A.A., Ahmed S.F., Farquharson C. Increased bone mass, altered trabecular architecture and modified growth plate organization in the growing skeleton of SOCS2 deficient mice. J. Cell. Physiol. 2009, 218:276-284.
24. Greenhalgh C.J., Rico-Bautista E., Lorentzon M., Thaus A.L., Morgan P.O., Willson T.A., Zervoudakis P., Metcalf D., Street I., Nicola N.A., Nash A.D., Fabri L.J., Norstedt G., Ohlsson C., Flores-Morales A., Alexander W.S., Hilton D.J. SOCS2 negatively regulates growth hormone action in vitro and in vivo. J. Clin. Invest. 2005, 115:397-406.
25. D'Ercole A.J. Expression of insulin-like growth factor-I in transgenic mice. Ann. N. Y. Acad. Sci. 1993, 692:149-160.
26. Mathews L.S., Hammer R.E., Behringer R.R., D'Ercole A.J., Bell G.I., Brinster R.L., Palmiter R.D. Growth enhancement of transgenic mice expressing human insulin-like growth factor I. Endocrinology 1988, 123:2827-2833.
27. Kasukawa Y., Baylink D.J., Guo R., Mohan S. Evidence that sensitivity to growth hormone (GH) is growth period and tissue type dependent: studies in GH-deficient lit/lit mice. Endocrinology 2003, 144:3950-3957.
28. Mohan S., Richman C., Guo R., Amaar Y., Donahue L.R., Wergedal J., Baylink D.J. Insulin-like growth factor regulates peak bone mineral density in mice by both growth hormone-dependent and -independent mechanisms. Endocrinology 2003, 144:929-936.
29. Godfrey P., Rahal J.O., Beamer W.G., Copeland N.G., Jenkins N.A., Mayo K.E. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat. Genet. 1993, 4:227-232.
30. Borrelli E., Heyman R.A., Arias C., Sawchenko P.E., Evans R.M. Transgenic mice with inducible dwarfism. Nature 1989, 339:538-541.
31. Sjogren K., Bohlooly Y.M., Olsson B., Coschigano K., Tornell J., Mohan S., Isaksson O.G., Baumann G., Kopchick J., Ohlsson C. Disproportional skeletal growth and markedly decreased bone mineral content in growth hormone receptor -/- mice. Biochem. Biophys. Res. Commun. 2000, 267:603-608.
32. Sims N.A., Clement-Lacroix P., Da Ponte F., Bouali Y., Binart N., Moriggl R., Goffin V., Coschigano K., Gaillard-Kelly M., Kopchick J., Baron R., Kelly P.A. Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5. J. Clin. Invest. 2000, 106:1095-1103.
33. Stevenson A.E., Evans B.A., Gevers E.F., Elford C., McLeod R.W., Perry M.J., El-Kasti M.M., Coschigano K.T., Kopchick J.J., Evans S.L., Wells T. Does adiposity status influence femoral cortical strength in rodent models of growth hormone deficiency?. Am. J. Physiol. Endocrinol. Metab. 2009, 296:E147-E156.
34. Udy G.B., Towers R.P., Snell R.G., Wilkins R.J., Park S.H., Ram P.A., Waxman D.J., Davey H.W. Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:7239-7244.
35. Neubauer H., Cumano A., Muller M., Wu H., Huffstadt U., Pfeffer K. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 1998, 93:397-409.
36. Parganas E., Wang D., Stravopodis D., Topham D.J., Marine J.C., Teglund S., Vanin E.F., Bodner S., Colamonici O.R., van Deursen J.M., Grosveld G., Ihle J.N. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 1998, 93:385-395.
37. Wang J., Zhou J., Powell-Braxton L., Bondy C. Effects of Igf1 gene deletion on postnatal growth patterns. Endocrinology 1999, 140:3391-3394.
38. Warburton C., Powell-Braxton L. Mouse models of IGF-I deficiency generated by gene targeting. Receptor 1995, 5:35-41.
39. Powell-Braxton L., Hollingshead P., Warburton C., Dowd M., Pitts-Meek S., Dalton D., Gillett N., Stewart T.A. IGF-I is required for normal embryonic growth in mice. Genes Dev. 1993, 7:2609-2617.
40. Powell-Braxton L., Hollingshead P., Giltinan D., Pitts-Meek S., Stewart T. Inactivation of the IGF-I gene in mice results in perinatal lethality. Ann. N. Y. Acad. Sci. 1993, 692:300-301.
41. Liu J.P., Baker J., Perkins A.S., Robertson E.J., Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 1993, 75:59-72.
42. Castilla-Cortazar I., Guerra L., Puche J.E., Munoz U., Barhoum R., Escudero E., Lavandera J.L. An experimental model of partial insulin-like growth factor-1 deficiency in mice. J. Physiol. Biochem. 2014, 70:129-139.
43. Bouabe H., Okkenhaug K. Gene targeting in mice: a review. Methods Mol. Biol. 2013, 1064:315-336.
44. Holzenberger M., Leneuve P., Hamard G., Ducos B., Perin L., Binoux M., Le Bouc Y. A targeted partial invalidation of the insulin-like growth factor I receptor gene in mice causes a postnatal growth deficit. Endocrinology 2000, 141:2557-2566.
45. Holzenberger M., Hamard G., Zaoui R., Leneuve P., Ducos B., Beccavin C., Perin L., Le Bouc Y. Experimental IGF-I receptor deficiency generates a sexually dimorphic pattern of organ-specific growth deficits in mice, affecting fat tissue in particular. Endocrinology 2001, 142:4469-4478.
46. Wang Y., Nishida S., Sakata T., Elalieh H.Z., Chang W., Halloran B.P., Doty S.B., Bikle D.D. Insulin-like growth factor-I is essential for embryonic bone development. Endocrinology 2006, 147:4753-4761.
47. Bikle D., Majumdar S., Laib A., Powell-Braxton L., Rosen C., Beamer W., Nauman E., Leary C., Halloran B. The skeletal structure of insulin-like growth factor I-deficient mice. J. Bone Miner. Res. 2001, 16:2320-2329.
48. He J., Rosen C.J., Adams D.J., Kream B.E. Postnatal growth and bone mass in mice with IGF-I haploinsufficiency. Bone 2006, 38:826-835.
49. Mohan S., Baylink D.J. Impaired skeletal growth in mice with haploinsufficiency of IGF-I: genetic evidence that differences in IGF-I expression could contribute to peak bone mineral density differences. J. Endocrinol. 2005, 185:415-420.
50. Stabnov L., Kasukawa Y., Guo R., Amaar Y., Wergedal J.E., Baylink D.J., Mohan S. Effect of insulin-like growth factor-1 (IGF-1) plus alendronate on bone density during puberty in IGF-1-deficient MIDI mice. Bone 2002, 30:909-916.
51. Constancia M., Hemberger M., Hughes J., Dean W., Ferguson-Smith A., Fundele R., Stewart F., Kelsey G., Fowden A., Sibley C., Reik W. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 2002, 417:945-948.
52. Lupu F., Terwilliger J.D., Lee K., Segre G.V., Efstratiadis A. Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev. Biol. 2001, 229:141-162.
53. Delahunty K.M., Shultz K.L., Gronowicz G.A., Koczon-Jaremko B., Adamo M.L., Horton L.G., Lorenzo J., Donahue L.R., Ackert-Bicknell C., Kream B.E., Beamer W.G., Rosen C.J. Congenic mice provide in vivo evidence for a genetic locus that modulates serum insulin-like growth factor-I and bone acquisition. Endocrinology 2006, 147:3915-3923.
54. Sjogren K., Sheng M., Moverare S., Liu J.L., Wallenius K., Tornell J., Isaksson O., Jansson J.O., Mohan S., Ohlsson C. Effects of liver-derived insulin-like growth factor I on bone metabolism in mice. J. Bone Miner. Res. 2002, 17:1977-1987.
55. Sjogren K., Liu J.L., Blad K., Skrtic S., Vidal O., Wallenius V., LeRoith D., Tornell J., Isaksson O.G., Jansson J.O., Ohlsson C. Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:7088-7092.
56. Yakar S., Canalis E., Sun H., Mejia W., Kawashima Y., Nasser P., Courtland H.W., Williams V., Bouxsein M., Rosen C., Jepsen K.J. Serum IGF-1 determines skeletal strength by regulating subperiosteal expansion and trait interactions. J. Bone Miner. Res. 2009, 24:1481-1492.
57. Yakar S., Liu J.L., Stannard B., Butler A., Accili D., Sauer B., LeRoith D. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:7324-7329.
58. Fan Y., Menon R.K., Cohen P., Hwang D., Clemens T., DiGirolamo D.J., Kopchick J.J., Le Roith D., Trucco M., Sperling M.A. Liver-specific deletion of the growth hormone receptor reveals essential role of growth hormone signaling in hepatic lipid metabolism. J. Biol. Chem. 2009, 284:19937-19944.
59. Cui Y., Hosui A., Sun R., Shen K., Gavrilova O., Chen W., Cam M.C., Gao B., Robinson G.W., Hennighausen L. Loss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration. Hepatology 2007, 46:504-513.
60. Shi S.Y., Martin R.G., Duncan R.E., Choi D., Lu S.Y., Schroer S.A., Cai E.P., Luk C.T., Hopperton K.E., Domenichiello A.F., Tang C., Naples M., Dekker M.J., Giacca A., Adeli K., Wagner K.U., Bazinet R.P., Woo M. Hepatocyte-specific deletion of Janus kinase 2 (JAK2) protects against diet-induced steatohepatitis and glucose intolerance. J. Biol. Chem. 2012, 287:10277-10288.
61. Nordstrom S.M., Tran J.L., Sos B.C., Wagner K.U., Weiss E.J. Liver-derived IGF-I contributes to GH-dependent increases in lean mass and bone mineral density in mice with comparable levels of circulating GH. Mol. Endocrinol. 2011, 25:1223-1230.
62. Ueki I., Ooi G.T., Tremblay M.L., Hurst K.R., Bach L.A., Boisclair Y.R. Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:6868-6873.
63. Courtland H.W., DeMambro V., Maynard J., Sun H., Elis S., Rosen C., Yakar S. Sex-specific regulation of body size and bone slenderness by the acid labile subunit. J. Bone Miner. Res. 2010, 25:2059-2068.
64. Yakar S., Rosen C.J., Beamer W.G., Ackert-Bicknell C.L., Wu Y., Liu J.L., Ooi G.T., Setser J., Frystyk J., Boisclair Y.R., LeRoith D. Circulating levels of IGF-1 directly regulate bone growth and density. J. Clin. Invest. 2002, 110:771-781.
65. Courtland H.W., Elis S., Wu Y., Sun H., Rosen C.J., Jepsen K.J., Yakar S. Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner. PLoS One 2011, 6.
66. Gong Z., Kennedy O., Sun H., Wu Y., Williams G.A., Klein L., Cardoso L., Matheny R.W., Hubbard G.B., Ikeno Y., Farrar R.P., Schaffler M.B., Adamo M.L., Muzumdar R.H., Yakar S. Reductions in serum IGF-1 during aging impair health span. Aging Cell 2014, 13:408-418.
67. Elis S., Courtland H.W., Wu Y., Fritton J.C., Sun H., Rosen C.J., Yakar S. Elevated serum IGF-1 levels synergize PTH action on the skeleton only when the tissue IGF-1 axis is intact. J. Bone Miner. Res. 2010, 25:2051-2058.
68. Elis S., Courtland H.W., Wu Y., Rosen C.J., Sun H., Jepsen K.J., Majeska R.J., Yakar S. Elevated serum levels of IGF-1 are sufficient to establish normal body size and skeletal properties even in the absence of tissue IGF-1. J. Bone Miner. Res. 2010, 25:1257-1266.
69. Elis S., Wu Y., Courtland H.W., Sun H., Rosen C.J., Adamo M.L., Yakar S. Increased serum IGF-1 levels protect the musculoskeletal system but are associated with elevated oxidative stress markers and increased mortality independent of tissue igf1 gene expression. Aging Cell 2011, 10:547-550.
70. Wu Y., Sun H., Basta-Pljakic J., Cardoso L., Kennedy O.D., Jasper H., Domene H., Karabatas L., Guida C., Schaffler M.B., Rosen C.J., Yakar S. Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor. J. Bone Miner. Res. 2013, 28:1575-1586.
71. Courtland H.W., Sun H., Beth-On M., Wu Y., Elis S., Rosen C.J., Yakar S. Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production. J. Bone Miner. Res. 2011, 26:761-768.
72. Elis S., Wu Y., Courtland H.W., Cannata D., Sun H., Beth-On M., Liu C., Jasper H., Domene H., Karabatas L., Guida C., Basta-Pljakic J., Cardoso L., Rosen C.J., Frystyk J., Yakar S. Unbound (bioavailable) IGF1 enhances somatic growth. Dis. Model. Mech. 2011, 4:649-658.
73. Moerth C., Schneider M.R., Renner-Mueller I., Blutke A., Elmlinger M.W., Erben R.G., Camacho-Hubner C., Hoeflich A., Wolf E. Postnatally elevated levels of insulin-like growth factor (IGF)-II fail to rescue the dwarfism of IGF-I-deficient mice except kidney weight. Endocrinology 2007, 148:441-451.
74. Tonella P., Fluck C.E., Mullis P.E. Insulin-like growth factor-I treatment in primary growth hormone insensitivity: effect of recombinant human IGF-I (rhIGF-I) and rhIGF-I/rhIGF-binding protein-3 complex. Horm. Res. Paediatr. 2010, 73:140-147.
75. Gevers E.F., van der Eerden B.C., Karperien M., Raap A.K., Robinson I.C., Wit J.M. Localization and regulation of the growth hormone receptor and growth hormone-binding protein in the rat growth plate. J. Bone Miner. Res. 2002, 17:1408-1419.
76. Jux C., Leiber K., Hugel U., Blum W., Ohlsson C., Klaus G., Mehls O. Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes. Endocrinology 1998, 139:3296-3305.
77. Smink J.J., Koster J.G., Gresnigt M.G., Rooman R., Koedam J.A., Van Buul-Offers S.C. IGF and IGF-binding protein expression in the growth plate of normal, dexamethasone-treated and human IGF-II transgenic mice. J. Endocrinol. 2002, 175:143-153.
78. Nilsson A., Carlsson B., Isgaard J., Isaksson O.G., Rymo L. Regulation by GH of insulin-like growth factor-I mRNA expression in rat epiphyseal growth plate as studied with in-situ hybridization. J. Endocrinol. 1990, 125:67-74.
79. Nilsson A., Isgaard J., Lindahl A., Dahlstrom A., Skottner A., Isaksson O.G. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate. Science 1986, 233:571-574.
80. Nilsson A., Swolin D., Enerback S., Ohlsson C. Expression of functional growth hormone receptors in cultured human osteoblast-like cells. J. Clin. Endocrinol. Metab. 1995, 80:3483-3488.
81. Nilsson A., Lindahl A., Eden S., Isaksson O.G. Demonstration of growth hormone receptors in cultured rat epiphyseal chondrocytes by specific binding of growth hormone and immunohistochemistry. J. Endocrinol. 1989, 122:69-77.
82. Vidal N.O., Ekberg S., Enerback S., Lindahl A., Ohlsson C. The CCAAT/enhancer-binding protein-alpha is expressed in the germinal layer of the growth plate: colocalisation with the growth hormone receptor. J. Endocrinol. 1997, 155:433-441.
83. Ohlsson C., Nilsson A., Isaksson O., Lindahl A. Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. Proc. Natl. Acad. Sci. U. S. A. 1992, 89:9826-9830.
84. Lindahl A., Nilsson A., Isaksson O.G. Effects of growth hormone and insulin-like growth factor-I on colony formation of rabbit epiphyseal chondrocytes at different stages of maturation. J. Endocrinol. 1987, 115:263-271.
85. Lindahl A., Isgaard J., Carlsson L., Isaksson O.G. Differential effects of growth hormone and insulin-like growth factor I on colony formation of epiphyseal chondrocytes in suspension culture in rats of different ages. Endocrinology 1987, 121:1061-1069.
86. Wang J., Zhou J., Bondy C.A. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. FASEB J. 1999, 13:1985-1990.
87. Gevers E.F., Hannah M.J., Waters M.J., Robinson I.C. Regulation of rapid signal transducer and activator of transcription-5 phosphorylation in the resting cells of the growth plate and in the liver by growth hormone and feeding. Endocrinology 2009, 150:3627-3636.
88. Cruickshank J., Grossman D.I., Peng R.K., Famula T.R., Oberbauer A.M. Spatial distribution of growth hormone receptor, insulin-like growth factor-I receptor and apoptotic chondrocytes during growth plate development. J. Endocrinol. 2005, 184:543-553.
89. Govoni K.E., Lee S.K., Chung Y.S., Behringer R.R., Wergedal J.E., Baylink D.J., Mohan S. Disruption of insulin-like growth factor-I expression in type IIalphaI collagen-expressing cells reduces bone length and width in mice. Physiol. Genomics 2007, 30:354-362.
90. Wang Y., Cheng Z., Elalieh H.Z., Nakamura E., Nguyen M.T., Mackem S., Clemens T.L., Bikle D.D., Chang W. IGF-1R signaling in chondrocytes modulates growth plate development by interacting with the PTHrP/Ihh pathway. J. Bone Miner. Res. 2011, 26:1437-1446.
91. Wu S., Yang W., De Luca F. Insulin-like growth factor independent effects of growth hormone on growth plate chondrogenesis and longitudinal bone growth. Endocrinology 2015.
92. Green H., Morikawa M., Nixon T. A dual effector theory of growth-hormone action. Differentiation 1985, 29:195-198.
93. Wang E., Wang J., Chin E., Zhou J., Bondy C.A. Cellular patterns of insulin-like growth factor system gene expression in murine chondrogenesis and osteogenesis. Endocrinology 1995, 136:2741-2751.
94. Shinar D.M., Endo N., Halperin D., Rodan G.A., Weinreb M. Differential expression of insulin-like growth factor-I (IGF-I) and IGF-II messenger ribonucleic acid in growing rat bone. Endocrinology 1993, 132:1158-1167.
95. Baker A.R., Hollingshead P.G., Pitts-Meek S., Hansen S., Taylor R., Stewart T.A. Osteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice. Mol. Cell. Biol. 1992, 12:5541-5547.
96. Zhao G., Monier-Faugere M.C., Langub M.C., Geng Z., Nakayama T., Pike J.W., Chernausek S.D., Rosen C.J., Donahue L.R., Malluche H.H., Fagin J.A., Clemens T.L. Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation. Endocrinology 2000, 141:2674-2682.
97. Brennan-Speranza T.C., Rizzoli R., Kream B.E., Rosen C., Ammann P. Selective osteoblast overexpression of IGF-I in mice prevents low protein-induced deterioration of bone strength and material level properties. Bone 2011, 49:1073-1079.
98. Jiang J., Lichtler A.C., Gronowicz G.A., Adams D.J., Clark S.H., Rosen C.J., Kream B.E. Transgenic mice with osteoblast-targeted insulin-like growth factor-I show increased bone remodeling. Bone 2006, 39:494-504.
99. Hall S.L., Chen S.T., Wergedal J.E., Gridley D.S., Mohan S., Lau K.H. Stem cell antigen-1 positive cell-based systemic human growth hormone gene transfer strategy increases endosteal bone resorption and bone loss in mice. J. Gene Med. 2011, 13:77-88.
100. Kesavan C., Wergedal J.E., Lau K.H., Mohan S. Conditional disruption of IGF-I gene in type 1alpha collagen-expressing cells shows an essential role of IGF-I in skeletal anabolic response to loading. Am. J. Physiol. Endocrinol. Metab. 2011, 301:E1191-E1197.
101. Govoni K.E., Wergedal J.E., Florin L., Angel P., Baylink D.J., Mohan S. Conditional deletion of insulin-like growth factor-I in collagen type 1alpha2-expressing cells results in postnatal lethality and a dramatic reduction in bone accretion. Endocrinology 2007, 148:5706-5715.
102. Zhang M., Xuan S., Bouxsein M.L., von Stechow D., Akeno N., Faugere M.C., Malluche H., Zhao G., Rosen C.J., Efstratiadis A., Clemens T.L. 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. 2002, 277:44005-44012.
103. Wang Y., Nishida S., Boudignon B.M., Burghardt A., Elalieh H.Z., Hamilton M.M., Majumdar S., Halloran B.P., Clemens T.L., Bikle D.D. IGF-I receptor is required for the anabolic actions of parathyroid hormone on bone. J. Bone Miner. Res. 2007, 22:1329-1337.
104. Sheng M.H., Zhou X.D., Bonewald L.F., Baylink D.J., Lau K.H. Disruption of the insulin-like growth factor-1 gene in osteocytes impairs developmental bone growth in mice. Bone 2013, 52:133-144.
105. Hoeflich A., Gotz W., Lichanska A.M., Bielohuby M., Tonshoff B., Kiepe D. Effects of insulin-like growth factor binding proteins in bone - a matter of cell and site. Arch. Physiol. Biochem. 2007, 113:142-153.
106. Ben Lagha N., Seurin D., Le Bouc Y., Binoux M., Berdal A., Menuelle P., Babajko S. Insulin-like growth factor binding protein (IGFBP-1) involvement in intrauterine growth retardation: study on IGFBP-1 overexpressing transgenic mice. Endocrinology 2006, 147:4730-4737.
107. Ben Lagha N., Menuelle P., Seurin D., Binoux M., Lebouc Y., Berdal A. Bone formation in the context of growth retardation induced by hIGFBP-1 overexpression in transgenic mice. Connect. Tissue Res. 2002, 43:515-519.
108. Eckstein F., Pavicic T., Nedbal S., Schmidt C., Wehr U., Rambeck W., Wolf E., Hoeflich A. Insulin-like growth factor-binding protein-2 (IGFBP-2) overexpression negatively regulates bone size and mass, but not density, in the absence and presence of growth hormone/IGF-I excess in transgenic mice. Anat. Embryol. (Berl) 2002, 206:139-148.
109. Silha J.V., Mishra S., Rosen C.J., Beamer W.G., Turner R.T., Powell D.R., Murphy L.J. Perturbations in bone formation and resorption in insulin-like growth factor binding protein-3 transgenic mice. J. Bone Miner. Res. 2003, 18:1834-1841.
110. Zhang M., Faugere M.C., Malluche H., Rosen C.J., Chernausek S.D., Clemens T.L. Paracrine overexpression of IGFBP-4 in osteoblasts of transgenic mice decreases bone turnover and causes global growth retardation. J. Bone Miner. Res. 2003, 18:836-843.
111. Salih D.A., Mohan S., Kasukawa Y., Tripathi G., Lovett F.A., Anderson N.F., Carter E.J., Wergedal J.E., Baylink D.J., Pell J.M. Insulin-like growth factor-binding protein-5 induces a gender-related decrease in bone mineral density in transgenic mice. Endocrinology 2005, 146:931-940.
112. Devlin R.D., Du Z., Buccilli V., Jorgetti V., Canalis E. Transgenic mice overexpressing insulin-like growth factor binding protein-5 display transiently decreased osteoblastic function and osteopenia. Endocrinology 2002, 143:3955-3962.
113. DeMambro V.E., Clemmons D.R., Horton L.G., Bouxsein M.L., Wood T.L., Beamer W.G., Canalis E., Rosen C.J. Gender-specific changes in bone turnover and skeletal architecture in igfbp-2-null mice. Endocrinology 2008, 149:2051-2061.
114. Yakar S., Rosen C.J., Bouxsein M.L., Sun H., Mejia W., Kawashima Y., Wu Y., Emerton K., Williams V., Jepsen K., Schaffler M.B., Majeska R.J., Gavrilova O., Gutierrez M., Hwang D., Pennisi P., Frystyk J., Boisclair Y., Pintar J., Jasper H., Domene H., Cohen P., Clemmons D., LeRoith D. Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism. FASEB J. 2009, 23:709-719.
115. Ning Y., Schuller A.G., Bradshaw S., Rotwein P., Ludwig T., Frystyk J., Pintar J.E. Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5. Mol. Endocrinol. 2006, 20:2173-2186.
116. Tanner S.J., Hefferan T.E., Rosen C.J., Conover C.A. Impact of pregnancy-associated plasma protein-a deletion on the adult murine skeleton. J. Bone Miner. Res. 2008, 23:655-662.
117. Dehority W., Halloran B.P., Bikle D.D., Curren T., Kostenuik P.J., Wronski T.J., Shen Y., Rabkin B., Bouraoui A., Morey-Holton E. Bone and hormonal changes induced by skeletal unloading in the mature male rat. Am. J. Physiol. 1999, 276:E62-E69.
118. Globus R.K., Bikle D.D., Morey-Holton E. The temporal response of bone to unloading. Endocrinology 1986, 118:733-742.
119. Turner C.H., Forwood M.R., Rho J.Y., Yoshikawa T. Mechanical loading thresholds for lamellar and woven bone formation. J. Bone Miner. Res. 1994, 9:87-97.
120. Rubin C.T., Lanyon L.E. Regulation of bone mass by mechanical strain magnitude. Calcif. Tissue Int. 1985, 37:411-417.
121. Fuchs R.K., Bauer J.J., Snow C.M. Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial. J. Bone Miner. Res. 2001, 16:148-156.
122. O'Connor J.A., Lanyon L.E., MacFie H. The influence of strain rate on adaptive bone remodelling. J. Biomech. 1982, 15:767-781.
123. Judex S., Gross T.S., Zernicke R.F. Strain gradients correlate with sites of exercise-induced bone-forming surfaces in the adult skeleton. J. Bone Miner. Res. 1997, 12:1737-1745.
124. Gross T.S., Edwards J.L., McLeod K.J., Rubin C.T. Strain gradients correlate with sites of periosteal bone formation. J. Bone Miner. Res. 1997, 12:982-988.
125. Jessop H.L., Rawlinson S.C., Pitsillides A.A., Lanyon L.E. Mechanical strain and fluid movement both activate extracellular regulated kinase (ERK) in osteoblast-like cells but via different signaling pathways. Bone 2002, 31:186-194.
126. Li J., Burr D.B., Turner C.H. Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading. Calcif. Tissue Int. 2002, 70:320-329.
127. Zaman G., Suswillo R.F., Cheng M.Z., Tavares I.A., Lanyon L.E. Early responses to dynamic strain change and prostaglandins in bone-derived cells in culture. J. Bone Miner. Res. 1997, 12:769-777.
128. Klein-Nulend J., van der Plas A., Semeins C.M., Ajubi N.E., Frangos J.A., Nijweide P.J., Burger E.H. Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. 1995, 9:441-445.
129. Rawlinson S.C., el-Haj A.J., Minter S.L., Tavares I.A., Bennett A., Lanyon L.E. Loading-related increases in prostaglandin production in cores of adult canine cancellous bone in vitro: a role for prostacyclin in adaptive bone remodeling?. J. Bone Miner. Res. 1991, 6:1345-1351.
130. Jessop H.L., Suswillo R.F., Rawlinson S.C., Zaman G., Lee K., Das-Gupta V., Pitsillides A.A., Lanyon L.E. Osteoblast-like cells from estrogen receptor alpha knockout mice have deficient responses to mechanical strain. J. Bone Miner. Res. 2004, 19:938-946.
131. Armour K.E., Armour K.J., Gallagher M.E., Godecke A., Helfrich M.H., Reid D.M., Ralston S.H. Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase. Endocrinology 2001, 142:760-766.
132. Zaman G., Pitsillides A.A., Rawlinson S.C., Suswillo R.F., Mosley J.R., Cheng M.Z., Platts L.A., Hukkanen M., Polak J.M., Lanyon L.E. Mechanical strain stimulates nitric oxide production by rapid activation of endothelial nitric oxide synthase in osteocytes. J. Bone Miner. Res. 1999, 14:1123-1131.
133. Pitsillides A.A., Rawlinson S.C., Suswillo R.F., Bourrin S., Zaman G., Lanyon L.E. Mechanical strain-induced NO production by bone cells: a possible role in adaptive bone (re)modeling?. FASEB J. 1995, 9:1614-1622.
134. Genetos D.C., Kephart C.J., Zhang Y., Yellowley C.E., Donahue H.J. Oscillating fluid flow activation of gap junction hemichannels induces ATP release from MLO-Y4 osteocytes. J. Cell. Physiol. 2007, 212:207-214.
135. Costessi A., Pines A., D'Andrea P., Romanello M., Damante G., Cesaratto L., Quadrifoglio F., Moro L., Tell G. Extracellular nucleotides activate Runx2 in the osteoblast-like HOBIT cell line: a possible molecular link between mechanical stress and osteoblasts' response. Bone 2005, 36:418-432.
136. Nakamura E., Uezono Y., Narusawa K., Shibuya I., Oishi Y., Tanaka M., Yanagihara N., Nakamura T., Izumi F. ATP activates DNA synthesis by acting on P2X receptors in human osteoblast-like MG-63 cells. Am. J. Physiol. Cell Physiol. 2000, 279:C510-C519.
137. Robling A.G., Niziolek P.J., Baldridge L.A., Condon K.W., Allen M.R., Alam I., Mantila S.M., Gluhak-Heinrich J., Bellido T.M., Harris S.E., Turner C.H. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J. Biol. Chem. 2008, 283:5866-5875.
138. Armstrong V.J., Muzylak M., Sunters A., Zaman G., Saxon L.K., Price J.S., Lanyon L.E. Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J. Biol. Chem. 2007, 282:20715-20727.
139. Lau K.H., Kapur S., Kesavan C., Baylink D.J. Up-regulation of the Wnt, estrogen receptor, insulin-like growth factor-I, and bone morphogenetic protein pathways in C57BL/6J osteoblasts as opposed to C3H/HeJ osteoblasts in part contributes to the differential anabolic response to fluid shear. J. Biol. Chem. 2006, 281:9576-9588.
140. Westendorf J.J., Kahler R.A., Schroeder T.M. Wnt signaling in osteoblasts and bone diseases. Gene 2004, 341:19-39.
141. Lee K.C., Jessop H., Suswillo R., Zaman G., Lanyon L.E. The adaptive response of bone to mechanical loading in female transgenic mice is deficient in the absence of oestrogen receptor-alpha and -beta. J. Endocrinol. 2004, 182:193-201.
142. Visconti L.A., Yen E.H., Johnson R.B. Effect of strain on bone nodule formation by rat osteogenic cells in vitro. Arch. Oral Biol. 2004, 49:485-492.
143. Damien E., Price J.S., Lanyon L.E. Mechanical strain stimulates osteoblast proliferation through the estrogen receptor in males as well as females. J. Bone Miner. Res. 2000, 15:2169-2177.
144. Cheng M., Zaman G., Rawlinson S.C., Mohan S., Baylink D.J., Lanyon L.E. Mechanical strain stimulates ROS cell proliferation through IGF-II and estrogen through IGF-I. J. Bone Miner. Res. 1999, 14:1742-1750.
145. Damien E., Price J.S., Lanyon L.E. The estrogen receptor's involvement in osteoblasts' adaptive response to mechanical strain. J. Bone Miner. Res. 1998, 13:1275-1282.
146. Hori Y., Katoh T., Hirakata M., Joki N., Kaname S., Fukagawa M., Okuda T., Ohashi H., Fujita T., Miyazono K., Kurokawa K. Anti-latent TGF-beta binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells. Kidney Int. 1998, 53:1616-1625.
147. Aguirre J.I., Plotkin L.I., Gortazar A.R., Millan M.M., O'Brien C.A., Manolagas S.C., Bellido T. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J. Biol. Chem. 2007, 282:25501-25508.
148. Sunters A., Armstrong V.J., Zaman G., Kypta R.M., Kawano Y., Lanyon L.E., Price J.S. Mechano-transduction in osteoblastic cells involves strain-regulated estrogen receptor alpha-mediated control of insulin-like growth factor (IGF) I receptor sensitivity to ambient IGF, leading to phosphatidylinositol 3-kinase/AKT-dependent Wnt/LRP5 receptor-independent activation of beta-catenin signaling. J. Biol. Chem. 2010, 285:8743-8758.
149. Reijnders C.M., Bravenboer N., Tromp A.M., Blankenstein M.A., Lips P. Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia. J. Endocrinol. 2007, 192:131-140.
150. Raab-Cullen D.M., Thiede M.A., Petersen D.N., Kimmel D.B., Recker R.R. Mechanical loading stimulates rapid changes in periosteal gene expression. Calcif. Tissue Int. 1994, 55:473-478.
151. Lean J.M., Mackay A.G., Chow J.W., Chambers T.J. Osteocytic expression of mRNA for c-fos and IGF-I: an immediate early gene response to an osteogenic stimulus. Am. J. Physiol. 1996, 270:E937-E945.
152. Gross T.S., Srinivasan S., Liu C.C., Clemens T.L., Bain S.D. Noninvasive loading of the murine tibia: an in vivo model for the study of mechanotransduction. J. Bone Miner. Res. 2002, 17:493-501.
153. Lau K.H., Baylink D.J., Zhou X.D., Rodriguez D., Bonewald L.F., Li Z., Ruffoni D., Muller R., Kesavan C., Sheng M.H. Osteocyte-derived insulin-like growth factor I is essential for determining bone mechanosensitivity. Am. J. Physiol. Endocrinol. Metab. 2013, 305:E271-E281.
154. Bikle D.D., Harris J., Halloran B.P., Morey-Holton E.R. Skeletal unloading induces resistance to insulin-like growth factor I. J. Bone Miner. Res. 1994, 9:1789-1796.
155. Sakata T., Wang Y., Halloran B.P., Elalieh H.Z., Cao J., Bikle D.D. Skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) by inhibiting activation of the IGF-I signaling pathways. J. Bone Miner. Res. 2004, 19:436-446.
156. Sakata T., Halloran B.P., Elalieh H.Z., Munson S.J., Rudner L., Venton L., Ginzinger D., Rosen C.J., Bikle D.D. Skeletal unloading induces resistance to insulin-like growth factor I on bone formation. Bone 2003, 32:669-680.
157. Kubota T., Elalieh H.Z., Saless N., Fong C., Wang Y., Babey M., Cheng Z., Bikle D.D. Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading. Acta Astronaut. 2013, 92:73-78.
158. Martinez C.S., Piazza V.G., Diaz M.E., Boparai R.K., Arum O., Ramirez M.C., Gonzalez L., Becu-Villalobos D., Bartke A., Turyn D., Miquet J.G., Sotelo A.I. GH/STAT5 signaling during the growth period in livers of mice overexpressing GH. J. Mol. Endocrinol. 2015, 54:171-184.
159. Graichen H., Lochmuller E.M., Wolf E., Langkabel B., Stammberger T., Haubner M., Renner-Muller I., Englmeier K.H., Eckstein F. A non-destructive technique for 3-D microstructural phenotypic characterisation of bones in genetically altered mice: preliminary data in growth hormone transgenic animals and normal controls. Anat. Embryol. (Berl) 1999, 199:239-248.
160. Behringer R.R., Lewin T.M., Quaife C.J., Palmiter R.D., Brinster R.L., D'Ercole A.J. Expression of insulin-like growth factor I stimulates normal somatic growth in growth hormone-deficient transgenic mice. Endocrinology 1990, 127:1033-1040.
161. Gao W.Q., Shinsky N., Ingle G., Beck K., Elias K.A., Powell-Braxton L. IGF-I deficient mice show reduced peripheral nerve conduction velocities and decreased axonal diameters and respond to exogenous IGF-I treatment. J. Neurobiol. 1999, 39:142-152.
162. Lembo G., Rockman H.A., Hunter J.J., Steinmetz H., Koch W.J., Ma L., Prinz M.P., Ross J., Chien K.R., Powell-Braxton L. Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency. J. Clin. Invest. 1996, 98:2648-2655.
163. DeChiara T.M., Robertson E.J., Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 1991, 64:849-859.
164. List E.O., Berryman D.E., Funk K., Jara A., Kelder B., Wang F., Stout M.B., Zhi X., Sun L., White T.A., LeBrasseur N.K., Pirtskhalava T., Tchkonia T., Jensen E.A., Zhang W., Masternak M.M., Kirkland J.L., Miller R.A., Bartke A., Kopchick J.J. Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles. Endocrinology 2014, 155:1793-1805.
165. Pintar J.E., Schuller A., Cerro J.A., Czick M., Grewal A., Green B. Genetic ablation of IGFBP-2 suggests functional redundancy in the IGFBP family. Prog. Growth Factor Res. 1995, 6:437-445.
166. Ning Y., Schuller A.G., Conover C.A., Pintar J.E. Insulin-like growth factor (IGF) binding protein-4 is both a positive and negative regulator of IGF activity in vivo. Mol. Endocrinol. 2008, 22:1213-1225.
167. Ning Y., Hoang B., Schuller A.G., Cominski T.P., Hsu M.S., Wood T.L., Pintar J.E. Delayed mammary gland involution in mice with mutation of the insulin-like growth factor binding protein 5 gene. Endocrinology 2007, 148:2138-2147.
168. Dai Z., Xing Y., Boney C.M., Clemmons D.R., D'Ercole A.J. Human insulin-like growth factor-binding protein-1 (hIGFBP-1) in transgenic mice: characterization and insights into the regulation of IGFBP-1 expression. Endocrinology 1994, 135:1316-1327.
169. Rajkumar K., Barron D., Lewitt M.S., Murphy L.J. Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 1995, 136:4029-4034.
170. Crossey P.A., Jones J.S., Miell J.P. Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance. Diabetes 2000, 49:457-465.
171. Watson C.S., Bialek P., Anzo M., Khosravi J., Yee S.P., Han V.K. Elevated circulating insulin-like growth factor binding protein-1 is sufficient to cause fetal growth restriction. Endocrinology 2006, 147:1175-1186.
172. Hoeflich A., Wu M., Mohan S., Foll J., Wanke R., Froehlich T., Arnold G.J., Lahm H., Kolb H.J., Wolf E. Overexpression of insulin-like growth factor-binding protein-2 in transgenic mice reduces postnatal body weight gain. Endocrinology 1999, 140:5488-5496.
173. Modric T., Silha J.V., Shi Z., Gui Y., Suwanichkul A., Durham S.K., Powell D.R., Murphy L.J. Phenotypic manifestations of insulin-like growth factor-binding protein-3 overexpression in transgenic mice. Endocrinology 2001, 142:1958-1967.
174. Miller B.S., Bronk J.T., Nishiyama T., Yamagiwa H., Srivastava A., Bolander M.E., Conover C.A. Pregnancy associated plasma protein-A is necessary for expeditious fracture healing in mice. J. Endocrinol. 2007, 192:505-513.
175. Qin X., Wergedal J.E., Rehage M., Tran K., Newton J., Lam P., Baylink D.J., Mohan S. Pregnancy-associated plasma protein-A increases osteoblast proliferation in vitro and bone formation in vivo. Endocrinology 2006, 147:5653-5661.