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Changes in serum runt-related transcription factor 2 levels after a 6-month treatment with recombinant human parathyroid hormone in patients with osteoporosis

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Abstract

Background: The mechanisms regulating the anabolic response of the skeleton for recombinant human PTH (1–34) [rhPTH (1–34)] administration has not been fully elucidated. Aim: The aim of this study was to evaluate the effect of rhPTH (1–34) on serum levels of runt-related transcription factor 2 (Runx2) in women with osteoporosis. Methods: Sixty postmenopausal women with osteoporosis (EO group) and 45 control subjects (NC group) were enrolled in this study. The EO group received daily injection of 20 µg rhPTH (1–34) plus oral 500 mg elemental calcium and 400 IU vitamin D3 for 6 months. Runx2 and Matrix metalloproteinase 13 (MMP-13) were measured with commercially available enzyme-linked immunosorbent assay kits. Bone mineral density (BMD) was also measured before and 6 months after rhPTH (1–34) treatment. Results: Serum total Ca2+, phosphate, and bone-specific alkaline phosphatase were significantly increased (p<0.05 or p<0.01), and the lumbar spine BMD (LS-BMD) was also increased by 4% in patients with osteoporosis after treatment with rhPTH (1–34) (p<0.05). On the contrary, serum Runx2 and MMP-13 were significantly decreased at post treatment (13.1% and 36.6%, respectively, p<0.05 and p<0.01). At baseline, serum Runx2 positively correlated with MMP-13 (r=0.74, p<0.01), the correction remained after adjusting for age and body mass index. Conclusion: The daily injection of rhPTH (1–34) was able to stimulate bone formation. The therapy of 20 µg rhPTH (1–34) for 6 months resulted in decrease of serum Runx2 and MMP-13. These changes might reflect the increase of active osteoblasts and the better bone homeostasis.

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References

  1. Porte D, Tuckermann J, Becker M, et al. Both AP-1 and Cbfa1 -like factors are required for the induction of interstitial collagenase by parathyroid hormone. Oncogene 1999, 18: 667–78.

    Article  PubMed  Google Scholar 

  2. Hodsman A, Bauer D, Dempster D, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocrine Rev 2005, 26: 688–703.

    Article  Google Scholar 

  3. Dobnig H, Turner RT. Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 1995, 136: 3632–8.

    PubMed  Google Scholar 

  4. Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 1999, 104: 439–46.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Lindsay R, Nieves J, Formica C, et al. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet 1997, 350: 550–5.

    Article  PubMed  Google Scholar 

  6. Schmidt IU, Dobnig H, Turner RT. Intermittent parathyroid hormone treatment increases osteoblast number, steady state messenger ribonucleic acid levels for osteocalcin, and bone formation in tibial metaphysis of hypophysectomized female rats. Endocrinology 1995, 136: 5127–33.

    PubMed  Google Scholar 

  7. Noda M, Rodan GA. Transcriptional regulation of osteopontin production in rat osteoblast-like cells by parathyroid hormone. J Cell Biol 1989, 108: 713–8.

    Article  PubMed  Google Scholar 

  8. Liang JD, Hock JM, Sandusky GE, Santerre RF, Onyia JE. Immunohistochemical localization of selected early response genes expressed in trabecular bone of young rats given hPTH 1–34. Calcif Tissue Int 1999, 65: 369–73.

    Article  PubMed  Google Scholar 

  9. Miles RR, Sluka JP, Santerre RF, et al. Dynamic regulation of RGS2 in bone: potential new insights into parathyroid hormone signaling mechanism. Endocrinology 2000, 141: 28–36.

    Article  PubMed  Google Scholar 

  10. Miles RR, Sluka JP, Halladay DL, et al. ADAMTS-1: a cellular disintegrin and metalloprotease with thrombospondin motifs is a target for parathyroid hormone in bone. Endocrinology 2000, 141: 4533–42.

    Article  PubMed  Google Scholar 

  11. Swarthout JT, D’Alonzo RC, Selvamurugan N, Partridge NC. Parathyroid hormone-dependent signaling pathways regulating genes in bone cells. Gene 2002, 282: 1–17.

    Article  PubMed  Google Scholar 

  12. Speck NA, Terryl S. A new transcription factor family associated with human leukemias. Crit Rev Eukaryot Gene Expr 1995, 5: 337–64.

    Article  PubMed  Google Scholar 

  13. Franceschi RT, Xiao G. Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem 2003, 88: 446–54.

    Article  PubMed  Google Scholar 

  14. Lian JB, Javed A, Zaidi SK, et al. Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr 2004, 14: 1–41.

    Article  PubMed  Google Scholar 

  15. Perinpanayagam H, Schneider G, Holtman K, Zaharias R, Stanford C. Altered Cbfa1 expression and biomineralization in an osteosarcoma cell line. J Orthop Res 2004, 22: 404–10.

    Article  PubMed  Google Scholar 

  16. Komori T, Yagi H, Nomura S, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997, 89: 755–64.

    Article  PubMed  Google Scholar 

  17. Otto F, Thornell AP, Crompton T, et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997, 89: 765–71.

    Article  PubMed  Google Scholar 

  18. Ducy P, Starbuck M, Priemel M, et al. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 1999, 13: 1025–36.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Erlebacher A, Filvaroff EH, Gitelman SE, Derynck R. Toward a molecular understanding of skeletal development. Cell 1995, 80: 371–8.

    Article  PubMed  Google Scholar 

  20. Hess J, Porte D, Munz C, Angel P. AP-1 and Cbfa/Runt physically interact and regulate parathyroid hormone-dependent MMP13 expression in osteoblasts through a new osteoblast-specific element 2/AP-1 composite element. J Biol Chem 2001, 276: 20029–38.

    Article  PubMed  Google Scholar 

  21. Jiménez MJ, Balbín M, López JM, Alvarez J, Komori T, López-Otín C. Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation. Mol Cell Biol 1999, 19: 4431–42.

    PubMed Central  PubMed  Google Scholar 

  22. Winchester SK, Selvamurugan N, D’Alonzo RC, Partridge NC. Developmental regulation of collagenase-3 mRNA in normal, differentiating osteoblasts through the activator protein-1 and the runt domain binding sites. J Biol Chem 2000, 275: 23310–8.

    Article  PubMed  Google Scholar 

  23. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001, 344: 1434–41.

    Article  PubMed  Google Scholar 

  24. Hwang JS, Tu ST, Yang TS, Chen JF, Wang CJ, Tsai KS. Teriparatide vs. calcitonin in the treatment of Asian postmenopausal women with established osteoporosis. Osteoporos Int 2006, 17: 373–8.

    Article  PubMed  Google Scholar 

  25. Hodsman AB, Fraher LJ, Watson PH, et al. A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 1997, 82: 620–8.

    PubMed  Google Scholar 

  26. Rittmaster RS, Bolognese M, Ettinger MP, et al. Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab 2000, 85: 2129–34.

    PubMed  Google Scholar 

  27. Krishnan V, Moore TL, Ma YL, et al. Parathyroid hormone bone anabolic action requires Cbfa1/Runx2-dependent signaling. Mol Endocrinol 2003, 17: 423–35.

    Article  PubMed  Google Scholar 

  28. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997, 89: 747–54.

    Article  PubMed  Google Scholar 

  29. Anastasilakis AD, Goulis DG, Polyzos SA, et al. Acute changes in serum osteoprotegerin and receptor activator for nuclear factor-kB ligand levels in women with established osteoporosis treated with teriparatide. Eur J Endocrinol 2008, 158: 411–5.

    Article  PubMed  Google Scholar 

  30. Liu W, Toyosawa S, Furuichi T, et al. Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol 2001, 155: 157–66.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Merciris D, Marty C, Collet C, de Vernejoul MC, Geoffroy V. Overexpression of the transcriptional factor Runx2 in osteoblasts abolishes the anabolic effect of parathyroid hormone in vivo. Am J Pathol 2007, 170: 1676–85.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 2003, 278: 50259–72.

    Article  PubMed  Google Scholar 

  33. Winchester SK, Bloch SR, Fiacco GJ, Partridge NC. Regulation of expression of collagenase-3 in normal, differentiating rat osteoblasts. J Cell Physiol 1999, 181: 479–88.

    Article  PubMed  Google Scholar 

  34. Franchimont N, Rydziel S, Delany AM, Canalis E. Interleukin-6 and its soluble receptor causes a marked induction of collagenase-3 expression in rat osteoblast cultures. J Biol Chem 1997, 272: 12144–50.

    Article  PubMed  Google Scholar 

  35. Kusano K, Miyaura C, Inada M, et al. Regulation of matrix metalloproteinases (MMP-2, -3, -9, and -13) by interleukin-1 and inter-leukin-6 in mouse calvaria: association of MMP induction with bone resorption. Endocrinology 1998, 139: 1338–45.

    PubMed  Google Scholar 

  36. Albala C, Yanez M, Devoto E, Sostin C, Zeballos L, Santos JL. Obesity as a protective factor for postmenopausal osteoporosis. Int J Obes Relat Metab Disord 1996, 20: 1027–32.

    PubMed  Google Scholar 

  37. Ribot C, Trémollières F, Pouillès JM. The effect of obesity on postmenopausal bone loss and the risk of osteoporosis. Adv Nutr Res 1994, 9: 257–71.

    PubMed  Google Scholar 

  38. Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA 2001, 286: 2815–22.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Biochemistry and the Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education, Chongqing Medical University College of Laboratory Medicine, Chongqing, China

    W. Zhu & L. Li MD

  2. Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    M. L. Yang & G. Y. Yang

  3. Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

    G. Boden

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  5. L. Li MD
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Correspondence to L. Li MD.

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Zhu, W., Yang, M.L., Yang, G.Y. et al. Changes in serum runt-related transcription factor 2 levels after a 6-month treatment with recombinant human parathyroid hormone in patients with osteoporosis. J Endocrinol Invest 35, 602–606 (2012). https://doi.org/10.3275/8110

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