Skip to main content
SpringerLink
Log in

Regulation of insulin-like growth factors and their binding proteins by thyroid stimulating hormone in human osteoblast-like (SaOS2) cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Thyroid stimulating hormone (TSH) is shown to have definite anabolic effects on skeletal metabolism. Previous studies have demonstrated that Insulin-like growth factors (IGF-I and IGF-II) and their six high affinity binding proteins (IGFBPs 1–6) regulate proliferation and differentiation of bone-forming osteoblasts. The current study was intended to determine whether the anabolic effects of TSH on human osteoblastic (SaOS2) cells are mediated through insulin-like growth factor system components. TSH given at 0.01 ng to 10 ng/ml dose levels for 24 and 48 h significantly increased human osteoblastic (SaOS2) cell proliferation and alkaline phosphatase activity, the differentiation marker. TSH significantly increased IGFs (IGF-I and IGF-II) mRNA expression after 6 and 24 h and their protein levels after 24 and 48 h of treatment, respectively. Unlike the IGFs, the IGFBPs responded differently to TSH treatment. Though there were some inconsistencies in the regulation of stimulatory IGF binding protein-3 and -5 by TSH treatment, there was an overall increase at the mRNA abundance and protein levels. Again, the inconsistency persisted at the regulation of the inhibitory IGFBPs 2, 4, and 6 especially at the level of mRNA expression due to TSH treatment, there is an overall decrease in the levels of IGFBP-2, 4, and 6 in the conditioned media (CM) of SaOS2 cell cultures. The IGFBP proteases which control the availability of IGFs are also regulated by hormones. Pregnancy-Associated Plasma Protein-A (PAPP-A) is responsible for the proteolysis of IGFBP-4. TSH treatment significantly unregulated the expression of PAPP-A both at mRNA and protein levels. In conclusion, TSH promotes human osteoblastic (SaOS2) cell proliferation and differentiation by upregulating IGFs and their stimulatory IGF binding proteins and down regulating the inhibitory IGF binding proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, Iqbal J, Eldeiry L, Rajendren G, Blair HC, Davies TF, Zaidi M (2003) TSH is a negative regulator of skeletal remodeling. Cell 115:151–162

    Article  PubMed  CAS  Google Scholar 

  2. Peeters RP, van der Deure WM, Visser TJ (2006) Genetic variation in thyroid hormonepathway genes: polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur J Endocrinol 155:655–662

    Article  PubMed  CAS  Google Scholar 

  3. Sampath TK, Simic P, Sendak R, Draca N, Bowe AE, O’Brien S, Schiavi SC, McPherson JM, Vukicevic S (2007) Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. J Bone Miner Res 22:849–859

    Article  PubMed  CAS  Google Scholar 

  4. Sun L, Vukicevic S, Baliram R, Yang G, Sendak R, McPherson J, Zhu LL, Iqbal J, Latif R, Natrajan A, Arabi A, Yamoah K, Moonga BS, Gabet Y, Davies TF, Bab I, Abe E, Sampath K, Zaidi M (2008) Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss. Proc Natl Acad Sci USA 11:4289–4294

    Article  Google Scholar 

  5. van der Deure WM, Uitterlinden AG, Hofman A, Rivadeneira F, Pols HA, Peeters RP et al (2008) Effects of serum TSH and FT4 levels and the TSHR-Asp727Glu polymorphism on bone: the Rotterdam Study. Clin Endocrinol 68:175–181

    Google Scholar 

  6. Iida K, Hino Y, Ohara T, Chihara K (2011) A case of myxedema coma caused by isolated thyrotropin stimulating hormone deficiency and Hashimoto’s thyroiditis. Endocr J 58:143–148

    Article  PubMed  CAS  Google Scholar 

  7. Ma R, Morshed S, Latif R, Zaidi M, Davies TF (2011) The influence of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on. Thyroid 21:897–906

    Article  PubMed  CAS  Google Scholar 

  8. Hase H, Ando T, Eldeiry L, Brebene A, Peng Y, Liu L, Amano H, Davies TF, Sun L, Zaidi M, Abe E (2006) TNFalpha mediates the skeletal effects of thyroid-stimulating hormone. Proc Natl Acad Sci USA 103:12849–12854

    Article  PubMed  CAS  Google Scholar 

  9. Canalis E (1994) Skeletal growth factors and aging. J Clin Endocrinol Metab 78:1009–1010

    Article  PubMed  CAS  Google Scholar 

  10. Mohan S, Baylink DJ (1999) IGF system components and their role in bone metabolism. In: Rosenfeld RG, Roberst C (eds) IGFs in health and disease. Humana Press, New York, pp 457–496

  11. Mohan S, Baylink DJ (1991) Bone growth factors. Clin Orthop 263:30–48

    PubMed  Google Scholar 

  12. Canalis E (1997) Insulin-like growth factors and osteoporosis. Bone 21:215–216

    Article  PubMed  CAS  Google Scholar 

  13. Gray TK, Mohan S, Linkhart TA, Baylink DJ (1989) Estradiol stimulates in vitro the secretion of insulin-like growth factors by the clonal osteoblastic cell line, UMR106. Biochem Biophys Res Commun 158:407–412

    Article  PubMed  CAS  Google Scholar 

  14. McCarthy TL, Centrella M, Canalis E (1989) Parathyroid hormone enhances the transcript and polypeptide levels of insulin-like growth factor I in osteoblast-enriched cultures from fetal rat bone. Endocrinology 124:1247–1253

    Article  PubMed  CAS  Google Scholar 

  15. Lakatos P, Caplice MD, Khanna V, Stern PH (1993) Thyroid hormones increase insulin-like growth factor-I content in the medium of rat bone tissue. J Bone Miner Res 8:1475–1481

    Article  PubMed  CAS  Google Scholar 

  16. Varga F, Rumpler M, Klaushofer K (1994) Thyroid hormones increase insulin-like growth factor mRNA levels in the clonal osteoblastic cell line MC3T3-E1. FEBS Lett 345:67–70

    Article  PubMed  CAS  Google Scholar 

  17. Chen TL, Mallory MB, Hintz RL (1991) Dexamethasone and 1,25(OH)2 vitamin D3 modulate the synthesis of insulin-like growth factor-I in osteoblast-like cells. Calcif Tissue Int 48:278–282

    Article  PubMed  CAS  Google Scholar 

  18. Canalis E (1996) Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis. Review. J Clin Endocrinol Metab 81:3441–3447

    Article  PubMed  CAS  Google Scholar 

  19. Cheng S-L, Yang JW, Rifas L, Zhang S-F, Avioli LV (1994) Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone. Endocrinology 134:277–286

    Article  PubMed  CAS  Google Scholar 

  20. Canalis E, Gabbitas B (1995) Skeletal growth factors regulate the synthesis of insulin-like growth factor binding protein-5 in bone cell cultures. J Biol Chem 270:10771–10776

    Article  PubMed  CAS  Google Scholar 

  21. Schmid C, Schlapfer I, Futo E, Waldvogel M, Schwander J, Zapf J, Froesch ER (1992) Triiodothyronine (T3) stimulates insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-2 production by rat osteoblasts in vitro. Acta Endocrinol 126:467–473

    PubMed  CAS  Google Scholar 

  22. Nakao Y, Hilliker S, Baylink DJ, Mohan S (1994) Studies on the regulation of insulin-like growth factor binding protein 3 secretion in human osteosarcoma cells in vitro. J Bone Miner Res 9:865–872

    Article  PubMed  CAS  Google Scholar 

  23. Srinivasan N, Baylink DJ, Sampath K, Mohan S (1997) Effects of inhibitors of signal transduction pathways on transforming growth factor-beta 1 and osteogenic protein-1-induced insulin-like growth factor binding protein-3 expression in human bone cells. J Cell Physiol 173:28–35

    Article  PubMed  CAS  Google Scholar 

  24. Ueland T, Bollerslev J, Hansen TB, Ebbesen EN, Mosekilde L, Brixen K (1999) Increased cortical bone content of insulin-like growth factors in acromegalic patients. J Clin Endocrinol Metab 84:123–127

    Article  PubMed  CAS  Google Scholar 

  25. Erclik MS, Mitchell J (2005) Activation of the insulin-like growth factor binding protein-5 promoter by parathyroid hormone in osteosarcoma cells requires activation of an activated protein-2 element. J Mol Endocrinol 34:713–722

    Article  PubMed  CAS  Google Scholar 

  26. Gabbitas B, Canalis E (1998) Insulin-like growth factors sustain insulin-like growth factor-binding protein-5 expression in osteoblasts. Am J Physiol 275:222–228

    Google Scholar 

  27. Mohan S, Nakao Y, Honda Y, Landale E, Leser U, Dony C et al (1995) lStudies on the mechanisms by which insulin-like growth factor (IGF) binding protein-4 (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. J Biol Chem 270:20424–20431

    Article  PubMed  CAS  Google Scholar 

  28. Mukherjee A, Rotwein P (2008) Insulin-like growth factor-binding protein-5 inhibits osteoblast differentiation and skeletal growth by blocking insulin-like growth factor actions. Mol Endocrinol 22:1238–1250

    Article  PubMed  CAS  Google Scholar 

  29. Backeljauw PF, Dai Z, Clemmons DR, D’Ercole AJ (1993) Synthesis and regulation of insulin-like growth factor binding protein-5 in FRTL-5 cells. Endocrinology 132:1677–1681

    Article  PubMed  CAS  Google Scholar 

  30. Kudo Y, Iwashita M, Iguchi T, Takeda Y, Hizuka N, Takano K, Muraki T (1997) Estrogen and parathyroid hormone regulate insulin-like growth factor binding protein-4 in SaOS-2 cells. Life Sci 61:165–170

    Article  PubMed  CAS  Google Scholar 

  31. Kveiborg M, Flyvbjerg A, Eriksen EF, Kassem M (2001) 1,25-Dihydroxyvitamin D3 stimulates the production of insulin-like growth factor-binding proteins-2, -3 and -4 in human bone marrow stromal cells. Eur J Endocrinol 144:549–557

    Article  PubMed  CAS  Google Scholar 

  32. Strohbach C, Kleinman S, Linkhart T, Amaar Y, Chen ST, Mohan S, Strong D (2008) Potential involvement of the interaction between insulin-like growth factor binding protein (IGFBP)-6 and LIM mineralization protein (LMP)-1 in regulating osteoblast differentiation. J Cell Biochem 104:1890–1905

    Article  PubMed  CAS  Google Scholar 

  33. Zhao YY, Guo L, Zhao XJ, Liu H, Lei T, Ma DJ, Gao XY (2009) Transcriptional activation of insulin-like growth factor binding protein 6 by 17beta-estradiol in SaOS-2 cells. Exp Mol Med 41:478–486

    Article  PubMed  CAS  Google Scholar 

  34. Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, Yates JR, Conover CA (1999) The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci 96:3149–3153

    Article  PubMed  CAS  Google Scholar 

  35. Kudo Y, Iwashita M, Iguchi T, Takeda Y, Hizuka N, Takano K, Muraki T (1997) Estrogen and parathyroid hormone regulate insulin-like growth factor binding protein-4 in SaOS-2 cells. Life Sci 61:165–170

    Article  PubMed  CAS  Google Scholar 

  36. Ortiz CO, Chen BK, Bale LK, Overgaard MT, Oxvig C, Conover CA (2003) Transforming growth factor-beta regulation of the insulin-like growth factor binding protein-4 protease system in cultured human osteoblasts. J Bone Miner Res 18:1066–1072

    Article  PubMed  CAS  Google Scholar 

  37. Matsumoto T, Gargosky SE, Kelley K, Rosenfeld RG (1996) Characterization of an insulin-like growth factor binding protein-5 protease produced by rat articular chondrocytes and a neuroblastoma cell line. Growth Regul 6:185–190

    PubMed  CAS  Google Scholar 

  38. Morgan SJ, Darling DC (1993) Animal cell culture. BIOS Scientific in Association with the Biochemical Society, London

    Google Scholar 

  39. Andersch MA, Szczypinski AJ (1947) Use of p-nitrophenylphosphate as the substrate in determination of serum acid phosphatase. Am J Clin Pathol 17:571–574

    PubMed  CAS  Google Scholar 

  40. Sila-Asna M, Bunyaratvej A, Maeda S, Kitaguchi H, Bunyaratavej N (2007) Osteoblast differentiation and bone formation gene expression in strontiuminducing bone marrow mesenchymal stem cell. Kobe J Med Sci 53:25–35

    PubMed  CAS  Google Scholar 

  41. Lowry OH, Rosebrough NJ, Farr AB, Randall RJ (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  42. Inoue M, Tawata M, Yokomori N, Endo T, Onaya T (1998) Expression of thryotropin receptor on clonal osteoblast-like rat osteosarcoma cells. Thyroid 8:1059–1064

    Article  PubMed  CAS  Google Scholar 

  43. Tsai JA, Janson A, Bucht E, Kindmark H, Marcus C, Stark A, Zemack HR, Torring O (2004) Weak evidence of thyrotropin receptors in primary cultures of human osteoblast-like cells. Calcif Tissue Int 74:486–491

    Article  PubMed  CAS  Google Scholar 

  44. Tramontano D, Moses AC, Ingbar SH (1988) The role of adenosine 3′,5′-monophosphate in the regulation of receptors for thyrotropin and insulin-like growth factor I in the FRTL5 rat thyroid follicular cell. Endocrinology 122:133–136

    Article  PubMed  CAS  Google Scholar 

  45. Baliram R, Latif R, Berkowitz J, Frid S, Colaianni G, Sun L, Zaidi M, Davies TF (2011) Thyroid-stimulating hormone induces a Wnt-dependent, feed-forward loop for osteoblastogenesis in embryonic stem cell cultures. Proc Natl Acad Sci USA 108:16277–16282

    Article  PubMed  CAS  Google Scholar 

  46. Billiard J, Grewal SS, Lukaesko L, Stork PJ, Rotwein P (2001) Hormonal control of insulin-like growth factor I gene transcription in human osteoblasts: dual actions of cAMP-dependent protein kinase on CCAAT/enhancer-binding protein delta. J Biol Chem 76:31238–31246

    Article  Google Scholar 

  47. Morimura T, Tsunekawa K, Kasahara T, Seki K, Ogiwara T, Mori M, Murakami M (2005) Expression of type 2 iodothyronine deiodinase in human osteoblast is stimulated by thyrotropin. Endocrinology 146:2077–2084

    Article  PubMed  CAS  Google Scholar 

  48. Phillips ID, Becks GP, Wang JF, Han VK, Hill DJ (1994) Hormonal regulation and biological actions of insulin-like growth factor binding proteins in isolated ovine thyroid follicles. Endocrinology 1994(134):1238–1246

    Article  Google Scholar 

  49. Imagawa M, Chiu R, Karin M (1987) Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell 51:251–260

    Article  PubMed  CAS  Google Scholar 

  50. Rivas M, Santisteban P (2003) TSH-activated signaling pathways in thyroid tumorigenesis. Mol Cell Endocrinol 213:31–45

    Article  PubMed  CAS  Google Scholar 

  51. Duan C, Liimatta MB, Bottum OL (1999) Insulin-like growth factor (IGF)-I regulates IGF-binding protein-5 gene expression through the phosphatidylinositol 3-kinase, protein kinase B/Akt, and p70 S6 kinase signaling pathway. J Biol Chem 274:37147–37153

    Article  PubMed  CAS  Google Scholar 

  52. Tanno B, Negroni A, Vitali R, Pirozzoli MC, Cesi V, Mancini C, Calabretta B, Raschellà G (2002) Expression of insulin-like growth factor-binding protein 5 in neuroblastoma cells is regulated at the transcriptional level by c-Myb and B-Myb via direct and indirect mechanisms. J Biol Chem 277:23172–23180

    Article  PubMed  CAS  Google Scholar 

  53. Zaballos MA, Garcia B, Santisteban P (2008) Gbetagamma dimers released in response to thyrotropin activate phosphoinositide 3-kinase and regulate gene expression in thyroid cells. Mol Endocrinol 22:1183–1199

    Article  PubMed  CAS  Google Scholar 

  54. Choi HS, Lee JH, Park JG, Lee YI (2002) Trichostatin A, a histone deacetylase inhibitor, activates the IGFBP-3 promoter by upregulating Sp1 activity in hepatoma cells: alteration of the Sp1/Sp3/HDAC1 multiprotein complex. Biochem Biophys Res Commun 296:1005–1012

    Article  PubMed  CAS  Google Scholar 

  55. Fanelli A, Grollman EF, Wang D, Philp NJ (2003) MCT1 and its accessory protein CD147 are differentially regulated by TSH in rat thyroid cells. Am J Physiol Endocrinol Metab 285:1223–1229

    Google Scholar 

  56. Wang E, Wang J, Chin E, Zhou J, Boundy CA (1995) Cellular patterns of insulin-like growth factor system gene expression in murine chondrogenesis and osteogenesis. Endocrinology 136:2741–2751

    Article  PubMed  CAS  Google Scholar 

  57. Laursen LS, Overgaard MT, Soe R, Boldt HB, Sottrup-Jensen L, Giudice LC, Conover CA, Oxvig C (2001) Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin- like growth factor binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of IGFBP-4 proteolysis by PAPP-A. FEBS Lett 504:36–40

    Article  PubMed  CAS  Google Scholar 

  58. Clemmons DR (1997) Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev 8:45–62

    Article  PubMed  CAS  Google Scholar 

  59. Marinaro JA, Neumann GM, Russo VC, Leeding KS, Bach LA (2000) O-glycosylation of insulin-like growth factor (IGF) binding protein-6 maintains high IGF-II binding affinity by decreasing binding to glycosaminoglycans and susceptibility to proteolysis. Eur J Biochem 267:5378–5386

    Article  PubMed  CAS  Google Scholar 

  60. Song BL, Qi W, Yang XY, Chang CC, Zhu JQ, Chang TY, Li BL (2001) Organization of human ACAT-2 gene and its cell-type-specific promoter activity. Biochem Biophys Res Commun 282:580–588

    Article  PubMed  CAS  Google Scholar 

  61. Guo L, Zhao YY, Zhao YY, Sun ZJ, Liu H, Zhang SL (2007) Toxic effects of TCDD on osteogenesis through altering IGFBP-6 gene expression in osteoblasts. Biol Pharm Bull 30:2018–2026

    Article  PubMed  CAS  Google Scholar 

  62. Maor G, Segev Y, Phillip M (1999) Testosterone stimulates insulin-like growth factor-I and insulin-like growth factor-I-receptor gene expression in the mandibular condyle—a model of endochondral ossification. Endocrinology 140:1901–1910

    Article  PubMed  CAS  Google Scholar 

  63. Bassett JH, Harvey CB, Williams GR (2003) Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions. Mol Cell Endocrinol 213:1–11

    Article  PubMed  CAS  Google Scholar 

  64. Conover CA, Bale LK, Clarkson JT, Tørring O (1993) Regulation of insulin-like growth factor binding protein-5 messenger ribonucleic acid expression and protein availability in rat osteoblast-like cells. Endocrinology 132:2525–2530

    Article  PubMed  CAS  Google Scholar 

  65. Zhang W, Deng ZL, Chen L, Zuo GW, Luo Q, Shi Q, Zhang BQ, Wagner ER, Rastegar F, Kim SH, Jiang W, Shen J, Huang E, Gao Y, Gao JL, Zhou JZ, Luo J, Huang J, Luo X, Bi Y, Su Y, Yang K, Liu H, Luu HH, Haydon RC, He TC, He BC (2010) Retinoic acids potentiate BMP9-induced osteogenic differentiation of mesenchymal progenitor cells. PLoS ONE 5:e11917

    Article  PubMed  Google Scholar 

  66. Scharla SH, Strong DD, Rosen C, Mohan S, Holick M, Baylink DJ, Linkhart TA (1993) 1,25-Dihydroxyvitamin D3 increases secretion of insulin-like growth factor binding protein-4 (IGFBP-4) by human osteoblast-like cells in vitro and elevates IGFBP-4 serum levels in vivo. J Clin Endocrinol Metab 77:1190–1197

    Article  PubMed  CAS  Google Scholar 

  67. Chevalley T, Strong DD, Mohan S, Baylink D, Linkhart TA (1996) Evidence for a role for insulin-like growth factor binding proteins in glucocorticoid inhibition of normal human osteoblast-like cell proliferation. Eur J Endocrinol 134:591–601

    Article  PubMed  CAS  Google Scholar 

  68. Mazziotti G, Sorvillo F, Piscopo M, Cioffi M, Pilla P, Biondi B, Iorio S, Giustina A, Amato G, Carella C (2005) Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma. J Bone Miner Res 20:480–486

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The financial support provided by the Indian Council of Medical Research (Ref: 53/13/2006 BMS), New Delhi, is gratefully acknowledged, The authors thank UGC-SAP, UGC-ASIST, and DST-FIST for creating infra structural facilities in the department. The authors also thank Dr. Robert C Baxter Kolling, the Institute of Medical Research, Australia, for his generous gift of IGFBP-3 antibody.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Dr. ALMPGIBMS, University of Madras, Chennai, 600 113, India

    G. Ramajayam, R. C. Vignesh, S. Karthikeyan, K. Senthil Kumar, G. D. Karthikeyan, S. Veni, J. Arunakaran, M. Michael Aruldhas & N. Srinivasan

  2. Department of Radiation Oncology, College of Medicine, Chungbuk National University, Cheongju, 361-763, South Korea

    M. Sridhar

Authors
  1. G. Ramajayam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. C. Vignesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Karthikeyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Senthil Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. D. Karthikeyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Veni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Sridhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Arunakaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. Michael Aruldhas
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. N. Srinivasan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. Srinivasan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramajayam, G., Vignesh, R.C., Karthikeyan, S. et al. Regulation of insulin-like growth factors and their binding proteins by thyroid stimulating hormone in human osteoblast-like (SaOS2) cells. Mol Cell Biochem 368, 77–88 (2012). https://doi.org/10.1007/s11010-012-1345-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-012-1345-4

Keywords

Search

Navigation