SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis

Journal of Bone and Mineral Research

Volumn 27, Issue 5, 2012, Pages 1055-1066

  Pass, Chloe ^a,b   MacRae, Vicky Elizabeth ^a   Huesa, Carmen ^a   Faisal Ahmed, S ^b   Farquharson, Colin ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b ROYAL HOSPITAL FOR SICK CHILDREN   (United Kingdom)

Author keywords

CHONDROCYTES; GH; GROWTH PLATE; SOCS2; STAT

Indexed keywords

GROWTH HORMONE; STAT1 PROTEIN; STAT3 PROTEIN; STAT5 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 1; SUPPRESSOR OF CYTOKINE SIGNALING 2; SUPPRESSOR OF CYTOKINE SIGNALING 3;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BONE GROWTH; CARTILAGE CELL; CELL PROLIFERATION; CHONDROGENESIS; CONTROLLED STUDY; FEMALE; LOSS OF FUNCTION MUTATION; MALE; METATARSAL BONE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION;

ANIMALS; BLOTTING, WESTERN; CELL PROLIFERATION; CELLS, CULTURED; CHONDROCYTES; CHONDROGENESIS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENOTYPE; GROWTH HORMONE; GROWTH PLATE; IMMUNOHISTOCHEMISTRY; INSULIN-LIKE GROWTH FACTOR I; MALE; METATARSAL BONES; MICE; MICE, KNOCKOUT; PHOSPHORYLATION; POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; SUPPRESSOR OF CYTOKINE SIGNALING PROTEINS;

EID: 84859890208     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.1544     Document Type: Article

References (77)

1. Salmon WD, Daughaday WH., A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med. 1957; 49: 825-36.
2. Isaksson OGP, Jansson JO, Gause IAM., Growth hormone stimulates longitudinal bone growth directly. Science. 1982; 216: 1237-9.
3. Nilsson A, Isgaard J, Lindahl A, Dahlström A, Skottner A, Isaksson OGP., Regulation by growth hormone of number of chondrocytes containing IGF-1 in rat growth plate. Science. 1986; 233: 571-4.
4. Stratikopoulos E, Szabolcs M, Dragatsis I, Klinakis A, Efstratiadis A., The hormonal action of IGF1 in postnatal mouse growth. Proc Natl Acad Sci USA. 2008; 105: 19378-83.
5. Yakar S, Liu JL, Butler A, Accili D, Sauer B, LeRoith D., Normal growth and development in the absence of hepatic insulin-like growth factor 1. Proc Natl Acad Sci USA. 1999; 96: 7324-9.
6. Sjögren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Törnell J, Isaksson OGP, Jansson JO, Ohlsson C., Liver-derived insulin-like growth factor I (IGF-1) is the principal source of IGF-1 in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA. 1999; 96: 7088-92.
7. Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A., Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol. 2001; 229: 141-62.
8. Baker J, Liu JP, Robertson EJ, Efstratiadis A., Role of insulin-like growth factors in embryonic and postnatal growth. Cell. 1993; 75: 73-82.
9. Liu JP, Baker J, Perkins AS, Robertson EJ, 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.
10. Darnell JE., STATs and gene regulation. Science. 1997; 277: 1630-5.
11. Herrington J, Smit LS, Schwartz J, Carter-Su C., The role of STAT proteins in growth hormone signaling. Oncogene. 2000; 19: 2585-97.
12. Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW., Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA. 1997; 94: 7239-44.
13. Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN., Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998; 93: 841-50.
14. Davey HW, McLachlan MJ, Wilkins RJ, Hilton DJ, Adams TE., STAT5b mediates the GH-induced expression of SOCS-2 and SOCS-3 mRNA in the liver. Mol Cell Endocrinol. 1999; 158: 111-6.
15. Sims NA, Clement-Lacroix P, Da Ponte F, Bouali Y, Binart N, Moriggl R, Goffin V, Coschigano K, Gaillard-Kelly M, Kopchick J, Baron R, Kelly PA., Bone homeostasis in growth hormone receptor-null mice is restored by IGF-1 but independent of Stat5. J Clin Invest. 2000; 106: 1095-103.
16. Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Rosenfeld RG., Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med. 2003; 349: 1139-47.
17. Milward A, Metherell L, Maamra M, Barahona MJ, Wilkinson IR, Camacho-Hübner C, Savage MO, Bidlingmaier M, Clark AJ, Ross RJ, Webb SM., Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction. J Clin Endocrinol Metab. 2004; 89: 1259-66.
18. Rosenfeld RG, Kofoed E, Buckway C, Little B, Woods KA, Tsubaki J, Pratt KA, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Hwa V., Identification of the first patient with a confirmed mutation of the JAK-STAT system. Pediatr Nephrol. 2005; 20: 303-5.
19. Tiulpakov A, Rubtsov P, Dedov I, Peterkova V, Bezlepkina O, Chrousos GP, Hochberg Z., A novel C-terminal growth hormone receptor (GHR) mutation results in impaired GHR-STAT5 but normal STAT-3 signaling. J Clin Endocrinol Metab. 2005; 90: 542-7.
20. Gevers EF, Hannah MJ, Waters MJ, Robinson ICAF., 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: 3627-36.
21. Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE, GH Insensitivity Syndrome Collaborative Group. Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-1 deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab. 2007; 92: 902-10.
22. Flores-Morales A, Greenhalgh CJ, Norstedt G, Rico-Bautista E., Negative regulation of growth hormone receptor signaling. Mol Endocrinol. 2006; 20: 241-53.
23. Starr R, Hilton DJ., Negative regulation of the JAK/STAT pathway. Bioessays. 1999; 21: 47-52.
24. Hilton DJ., Negative regulators of cytokine signal transduction. Cell Mol Life Sci. 1999; 55: 1568-77.
25. Rico-Bautista E, Flores-Morales A, Fernández-Pérez L., Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions. Cytokine Growth Factor Rev. 2006; 17: 431-9.
26. Pass C, Macrae VE, Ahmed SF, Farquharson C., Inflammatory cytokines and the GH/IGF-1 axis: novel actions on bone growth. Cell Biochem Funct. 2009; 27: 119-27.
27. Tollet-Egnell P, Flores-Morales A, Stavreus-Evers A, Sahlin L, Norstedt G., Growth hormone regulation of SOCS-2, SOCS-3, and CIS messenger ribonucleic acid expression in the rat. Endocrinology. 1999; 140: 3693-704.
28. Metcalf D, Greenhalgh CJ, Viney E, Willson TA, Starr R, Nicola NA, Hilton DJ, Alexander WS., Gigantism in mice lacking suppressor of cytokine signaling-2. Nature. 2000; 405: 1069-73.
29. Roberts AW, Robb L, Rakar S, Hartley L, Cluse L, Nicola NA, Metcalf D, Hilton DJ, Alexander WS., Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. Proc Natl Acad Sci USA. 2001; 98: 9324-9.
30. Lorentzon M, Greenhalgh CJ, Mohan S, Alexander WS, Ohlsson C., Reduced bone mineral density in SOCS-2-deficient mice. Pediatr Res. 2005; 57: 223-6.
31. Macrae VE, Horvat S, Pells SC, Dale H, Collinson RS, Pitsillides AA, Ahmed SF, 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: 276-84.
32. Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN., SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell. 1999; 98: 609-16.
33. Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JN., SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999; 98: 617-27.
34. Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, Sprigg NS, Corbin JE, Cornish AL, Darwiche R, Owczarek CM, Kay TWH, Nicola NA, Hertzog PJ, Metcalf D, Hilton DJ., SOCS1 is a critical inhibitor of interferon [gamma] signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell. 1999; 98: 597-608.
35. Turnley AM., Role of SOCS2 in growth hormone actions. Trends Endocrinol Metab. 2005; 16: 53-8.
36. Greenhalgh CJ, Bertolino P, Asa SL, Metcalf D, Corbin JE, Adams TE, Davey HW, Nicola NA, Hilton DJ, Alexander WS., Growth enhancement in suppressor of cytokine signaling 2 (SOCS-2)-deficient mice is dependent on signal transducer and activator of transcription 5b (STAT5b). Mol Endocrinol. 2002; 16: 1394-406.
37. Chagin AS, Lindberg MK, Andersson N, Moverare S, Gustafsson JA, Sävendahl L, Ohlsson C., Estrogen receptor-beta inhibits skeletal growth and has the capacity to mediate growth plate fusion in female mice. J Bone Miner Res. 2004; 19: 72-7.
38. Rawlinson SCF, Murray DH, Mosley JR, Wright CDP, Bredl JC, Saxon LK, Loveridge N, Leterrier C, Constantin P, Farquharson C, Pitsillides AA., Genetic selection for fast growth generates bone architecture characterised by enhanced periosteal expansion and limited consolidation of the cortices but a diminution in the early responses to mechanical loading. Bone. 2009; 45: 357-66.
39. Owen HC, Ahmed SF, Farquharson C., Chondrocyte p21(WAF1/CIP1) expression is increased by dexamethasone but does not contribute to dexamethasone-induced growth retardation in vivo. Calcif Tissue Int. 2009; 85: 326-34.
40. Jacquet R, Hillyer J, Landis WJ., Analysis of connective tissues by laser capture microdissection and reverse transcriptase-polymerase chain reaction. Anal Biochem. 2005; 337: 22-34.
41. Erben RG., Bone-labeling techniques. In:, An YH, Martin KL, editors. Handbook of histology methods for bone and cartilage. Totowa, NJ: Humana Press; 2003. p. 99-117.
42. Lefebvre V, Garofalo S, Zhou G, Metsäranta M, Vuorio E, de Crombrugghe B., Characterization of primary cultures of chondrocytes from type II collagen/[beta]-galactosidase transgenic mice. Matrix Biol. 1994; 14: 329-35.
43. Mushtaq T, Bijman P, Ahmed SF, Farquharson C., Insulin-like growth factor-I augments chondrocyte hypertrophy and reverses glucocorticoid-mediated growth retardation in fetal mice metatarsal cultures. Endocrinology. 2004; 145: 2478-86.
44. Macrae VE, Burdon T, Ahmed SF, Farquharson C., Ceramide inhibition of chondrocyte proliferation and bone growth is IGF-1 independent. J Endocrinol. 2006; 191: 369-77.
45. Mushtaq T, Farquharson C, Seawright E, Ahmed SF., Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line. J Endocrinol. 2002; 175: 705-13.
46. Enomoto H, Enomoto-Iwamoto M, Iwamoto M, Nomura S, Himeno M, Kitamura Y, Kishimoto T, Komori T., Cbfa1 is a positive regulatory factor in chondrocyte maturation. J Biol Chem. 2000; 275: 8695-702.
47. Farquharson C, Lester D, Seawright E, Jefferies D, Houston B., Microtubules are potential regulators of growth-plate chondrocyte differentiation and hypertrophy. Bone. 1999; 25: 405-12.
48. Houston B, Seawright E, Jefferies D, Hoogland E, Lester D, Whitehead C, Farquharson C., Identification and cloning of a novel phosphatase expressed at high levels in differentiating growth plate chondrocytes. Biochim Biophys Acta. 1999; 1448: 500-6.
49. Han YL, Leaman DW, Watling D, Rogers NC, Groner B, Kerr IM, Wood WI, Stark GR., Participation of JAK and STAT proteins in growth hormone-induced signaling. J Biol Chem. 1996; 271: 5947-52.
50. Brooks AJ, Wooh JW, Tunny KA, Waters MJ., Growth hormone receptor; mechanism of action. Int J Biochem Cell Biol. 2008; 40: 1984-9.
51. Waters MJ, Hoang HN, Fairlie DP, Pelekanos RA, Brown RJ., New insights into growth hormone action. J Mol Endocrinol. 2006; 36: 1-7.
52. Smit LS, Meyer DJ, Billestrup N, Norstedt G, Schwartz J, Carter-Su C., The role of the growth hormone (GH) receptor and JAK1 and JAK2 kinases in the activation of Stats 1, 3, and 5 by GH. Mol Endocrinol. 1996; 10: 519-33.
53. Starr R, Metcalf D, Elefanty AG, Brysha M, Willson TA, Nicola NA, Hilton DJ, Alexander WS., Liver degeneration and lymphoid deficiencies in mice lacking suppressor of cytokine signaling-1. Proc Natl Acad Sci USA. 1998; 95: 14395-9.
54. Macrae VE, Ahmed SF, Mushtaq T, Farquharson C., IGF-1 signaling in bone growth: inhibitory actions of dexamethasone and IL-1[beta]. Growth Horm IGF Res. 2007; 17: 435-9.
55. Coxam V, Miller MA, Bowman MB, Miller SC., Ontogenesis of IGF regulation of longitudinal bone growth in rat metatarsal rudiments cultured in serum-free medium. Arch Physiol Biochem. 1996; 104: 173-9.
56. Martensson K, Chrysis D, Savendahl L., Interleukin-1beta and TNF-alpha act in synergy to inhibit longitudinal growth in fetal rat metatarsal bones. J Bone Miner Res. 2004; 19: 1805-12.
57. Paukku K, Silvennoinen O., STATs as critical mediators of signal transduction and transcription: lessons learned from STAT5. Cytokine Growth Factor Rev. 2004; 15: 435-55.
58. Rico-Bautista E, Greenhalgh CJ, Tollet-Egnell P, Hilton DJ, Alexander WS, Norstedt G, Flores-Morales A., Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic changes that partially overlap with growth hormone-dependent effects. Mol Endocrinol. 2005; 19: 781-93.
59. 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 USA. 1992; 89: 9826-30.
60. Govoni KE, Lee SK, Chung YS, Behringer RR, Wergedal JE, Baylink DJ, 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: 354-62.
61. Klammt J, Pfäffle R, Werner H, Kiess W., IGF signaling defects as causes of growth failure and IUGR. Trends Endocrinol Metab. 2008; 19: 197-205.
62. Hoshi K, Ogata N, Shimoaka T, Terauchi Y, Kadowaki T, Kenmotsu S, Chung UI, Ozawa H, Nakamura K, Kawaguchi H., Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage. J Bone Miner Res. 2004; 19: 214-23.
63. Decker T, Kovarik P., Serine phosphorylation of STATs. Oncogene. 2000; 19: 2628-37.
64. Stahl N, Farruggella TJ, Boulton TG, Zhong Z, Darnell JE, Yancopoulos GD., Choice of Stats and other substrates specified by modular tyrosine-based motifs in cytokine receptors. Science. 1995; 267: 1349-53.
65. Greenhalgh CJ, Metcalf D, Thaus AL, Corbin JE, Uren R, Morgan PO, Fabri LJ, Zhang JG, Martin HM, Willson TA, Billestrup N, Nicola NA, Baca M, Alexander WS, Hilton DJ., Biological evidence that SOCS-2 can act either as an enhancer or suppressor of growth hormone signaling. J Biol Chem. 2002; 277: 40181-4.
66. Favre H, Benhamou A, Finidori J, Kelly PA, Edery M., Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction. FEBS Lett. 1999; 453: 63-6.
67. Dey BR, Spence SL, Nissley P, Furlanetto RW., Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor. J Biol Chem. 1998; 273: 24095-101.
68. Scheven BA, Hamilton NJ., Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone. Acta Endocrinol. 1991; 124: 602-7.
69. Shoba LN, Newman M, Liu W, Lowe WL Jr., LY 294002, an inhibitor of phosphatidylinositol 3-kinase, inhibits GH-mediated expression of the IGF-1 gene in rat hepatocytes. Endocrinology. 2001; 142: 3980-6.
70. Parker EA, Hegde A, Buckley M, Barnes KM, Baron J, Nilsson O., Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage. J Endocrinol. 2007; 194: 31-40.
71. Wang J, Zhou J, Cheng CM, Kopchick JJ, Bondy CA., Evidence supporting dual, IGF-1-independent and IGF-1-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol. 2004; 180: 247-55.
72. Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CKW, Low TH, Leong GM, Ross RJM, Ho KKY., Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proc Natl Acad Sci USA. 2003; 100: 1016-21.
73. Leong GM, Moverare S, Brce J, Doyle N, Sjögren K, Dahlman-Wright K, Gustafsson JA, Ho KKY, Ohlsson C, Leung KC., Estrogen up-regulates hepatic expression of suppressors of cytokine signaling-2 and -3 in vivo and in vitro. Endocrinology. 2004; 145: 5525-31.
74. Gevers EF, van der Eerden BC, Karperien M, Raap AK, Robinson IC, Wit JM., Localization and regulation of the growth hormone receptor and growth hormone-binding protein in the rat growth plate. J Bone Miner Res. 2002; 17: 1408-19.
75. Kember NF., Comparative patterns of cell division in epiphyseal cartilage plates in the rabbit. J Anat. 1985; 142: 185-90.
76. Breur GJ, VanEnkevort A, Farnum CE, Wilsman NJ., Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates. J Orthop Res. 1991; 9: 348-59.
77. Wang J, Zhou J, Bondy CA., Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. FASEB J. 1999; 13: 1985-90.