Rheumatology International

, Volume 29, Issue 6, pp 667–672 | Cite as

Normal and osteoporotic human osteoblast behaviour after 1,25-dihydroxy-vitamin D3 stimulation

  • N. Maruotti
  • A. Corrado
  • M. Grano
  • S. Colucci
  • F. P. Cantatore
Original Article

Abstract

In order to examine the effects of vitamin D on osteoblast function and to evaluate if osteoporotic and normal osteoblasts show a different behaviour in response to vitamin D, this report investigates the changes in osteocalcin production, after 1,25-dihydroxy-vitamin D3 stimulation of cultured osteoblasts derived from osteoporotic patients. Our results indicate an inadequate osteoblastic function in osteoporosis and demostrate that 1,25-dihydroxy-vitamin D3 can stimulate the metabolic activity of human osteoblasts in vitro. Considering that osteoporotic bone samples were representative of senile osteoporosis, our results may indicate a different metabolic phenotype in osteoporotic osteoblasts compared with normal osteoblasts. The increased osteocalcin production after 1,25-dihydroxy-vitamin D3 stimulation of osteoporotic osteoblasts suggests a reduced, but not absent, anabolic function in senile osteoporotic osteoblasts. The results of this study confirm the validity of vitamin D3 to treat senile osteoporosis and suggest the need of higher vitamin D3 intake in senile osteoporotic patients than in younger subjects.

Keywords

Osteoblasts Osteocalcin Osteoporosis Vitamin D 

References

  1. 1.
    Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325. doi:10.1172/JCI27071 PubMedCrossRefGoogle Scholar
  2. 2.
    Ebeling PR, Atley LM, Guthrie JR et al (1996) Bone turnover markers and bone density across the menopausal transition. J Clin Endocrinol Metab 81:3366–3371. doi:10.1210/jc.81.9.3366 PubMedCrossRefGoogle Scholar
  3. 3.
    Boyden LM, Mao J, Belsky J et al (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346:1513–1521. doi:10.1056/NEJMoa013444 PubMedCrossRefGoogle Scholar
  4. 4.
    Horwitz MC, Lorenzo JA (2002) Local regulators of bone: IL-1, TNF, lymphotoxin, interferon-γ, IL-8, IL-10, IL-4, the LIF/IL-6 family, and additional cytokines. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology. Academic Press, San Diego, pp 961–977Google Scholar
  5. 5.
    Langdahl BL, Carstens M, Stenkjaer L et al (2002) Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res 17:1245–1255. doi:10.1359/jbmr.2002.17.7.1245 PubMedCrossRefGoogle Scholar
  6. 6.
    Langdahl BL, Carstens M, Stenkjaer L et al (2003) Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone 32:297–310. doi:10.1016/S8756-3282(02)00971-7 PubMedCrossRefGoogle Scholar
  7. 7.
    Robey PG, Boskey AL (1995) The biochemistry of bone. In: Marcus R, Feldman D, Bilezikian JP, Kelsey J (eds) Osteoporosis. Academic Press, New York, pp 95–183Google Scholar
  8. 8.
    Boskey AL (1996) Matrix proteins and mineralization: an overview. Connect Tissue Res 35:357–363. doi:10.3109/03008209609029212 PubMedCrossRefGoogle Scholar
  9. 9.
    Boskey AL (1998) Biomineralization: conflicts, challenges, and opportunities. J Cell Biochem Suppl 30–31:83–91. doi:10.1002/(SICI)1097-4644(1998)72:30/31+<83::AID-JCB12>3.0.CO;2-FPubMedCrossRefGoogle Scholar
  10. 10.
    Whyte MP (1994) Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev 15:439–461. doi:10.1210/er.15.4.439 PubMedGoogle Scholar
  11. 11.
    Rehman MTA, Hoyland JA, Denton J et al (1995) Histomorphometric classification of postmenopausal osteoporosis–implications for the management of osteoporosis. J Clin Pathol 48:229–235. doi:10.1136/jcp.48.3.229 PubMedCrossRefGoogle Scholar
  12. 12.
    Bennett JH, Joyner CJ, Triffitt JT et al (1991) Adipocytic cells cultured from marrow have osteogenic potential. J Cell Sci 99:131–139PubMedGoogle Scholar
  13. 13.
    Beresford JN, Bennett JH, Devlin C et al (1992) Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell-cultures. J Cell Sci 102:341–351PubMedGoogle Scholar
  14. 14.
    Gori F, Thomas T, Hicok KC et al (1999) Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation. J Bone Miner Res 14:1522–1535. doi:10.1359/jbmr.1999.14.9.1522 PubMedCrossRefGoogle Scholar
  15. 15.
    Burkhardt R, Kettner G, Bohm W et al (1987) Changes in trabecular bone, hematopoiesis and bone-marrow vessels in aplastic-anemia, primary osteoporosis, and old-age—a comparative histomorphometric study. Bone 8:157–164. doi:10.1016/8756-3282(87)90015-9 PubMedCrossRefGoogle Scholar
  16. 16.
    Byers RJ, Hoyland JA, Braidman IP (2001) Osteoporosis in men: a cellular endocrine perspective of an increasingly common clinical problem. J Endocrinol 168:353–362. doi:10.1677/joe.0.1680353 PubMedCrossRefGoogle Scholar
  17. 17.
    Chan GK, Duque G (2002) Age-related bone loss: old bone, new facts. Gerontology 48:62–71. doi:10.1159/000048929 PubMedCrossRefGoogle Scholar
  18. 18.
    Raisz LG (1999) Physiology and pathophysiology of bone remodeling. Clin Chem 45:1353–1358PubMedGoogle Scholar
  19. 19.
    Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501. doi:10.1210/er.22.4.477 PubMedCrossRefGoogle Scholar
  20. 20.
    Gurlek A, Pittelkow MR, Kumar R (2002) Modulation of growth factor/cytokine synthesis and signaling by 1,25-dihydroxyvitamin D3: implications in cell growth and differentiation. Endocr Rev 23:763–786. doi:10.1210/er.2001-0044 PubMedCrossRefGoogle Scholar
  21. 21.
    Takasu H, Sugita A, Uchiyama Y et al (2006) c-Fos proteina s a target of anti-clastogenic action of vitamin D, and synthesis of new analogs. J Clin Invest 116:528–535. doi:10.1172/JCI24742 PubMedCrossRefGoogle Scholar
  22. 22.
    Reichel H, Koeffler HP, Norman AW (1989) The role of the vitamin D endocrine system in health and disease. N Engl J Med 320:980–991PubMedGoogle Scholar
  23. 23.
    Veenstra TD, Pittelkow MR, Kumar R (1999) Regulation of cellular growth by 1,25-dihydroxyvitamin D3-mediated growth factor expression. News Physiol Sci 14:37–40PubMedGoogle Scholar
  24. 24.
    Matsumoto T, Igarashi C, Takeuchi Y et al (1991) Stimulation by 1,25-dihydroxyvitamin D3 of in vitro mineralization induced by osteoblast-like MC3T3-E1 cells. Bone 12:27–32. doi:10.1016/8756-3282(91)90051-J PubMedCrossRefGoogle Scholar
  25. 25.
    Ishida H, Bellows CG, Aubin JE et al (1993) Characterization of the 1,25-(OH)2D3-induced inhibition of bone nodule formation in long-term cultures of fetal rat calvaria cells. Endocrinology 132:61–66. doi:10.1210/en.132.1.61 PubMedCrossRefGoogle Scholar
  26. 26.
    Zambonin G, Colucci S, Cantatore FP et al (1998) Response of human osteoblasts to polymethylmetacrylatein vitro. Calcif Tissue Int 62:362–365. doi:10.1007/s002239900445 PubMedCrossRefGoogle Scholar
  27. 27.
    Jones G, Hogan DB, Yendt E et al (1996) Vitamin D metabolites and analogs in the treatment of osteoporosis. Can Med Assoc J 155:955–961Google Scholar
  28. 28.
    Beresford JN, Gallagher JA, Russell RG (1986) 1,25-Dihydroxyvitamin D3 and human bone-derived cells in vitro: effects on alkaline phosphatase, type I collagen and proliferation. Endocrinology 119:1176–1179Google Scholar
  29. 29.
    Wong MM, Rao LG, Ly H et al (1990) Long-term effects of physiologic concentrations of dexamethasone on human bone-derived cells. Bone Min Res 5:803–813Google Scholar
  30. 30.
    Shakoori AR, Van Wijnen AJ, Bortell R et al (1994) Variations in vitamin D receptor transcription factor complexes associated with the osteocalcin gene vitamin D responsive element in osteoblasts and osteosarcoma cells. Cell Biochem 55:218–229. doi:10.1002/jcb.240550209 CrossRefGoogle Scholar
  31. 31.
    Rao LG, Wylie JN, Kung Sutherland MS et al (1996) 17 beta-oestradiol enhances the stimulatory effect of 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity in human osteosarcoma SaOS-2 cells in a differentiation-dependent manner. J Endocr 148:181–187. doi:10.1677/joe.0.1480181 PubMedCrossRefGoogle Scholar
  32. 32.
    Sutherland MK, Hui DU, Rao LG et al (1996) Immunohistochemical localization of the estrogen receptor in human osteoblastic SaOS-2 cells: association of receptor levels with alkaline phosphatase activity. Bone 18:361–369. doi:10.1016/8756-3282(96)00016-6 PubMedCrossRefGoogle Scholar
  33. 33.
    Kim H, Chen TL (1989) 1,25-dihydroxyvitamin D3 interaction with dexamethasone and retinoic acid: effects on procollagen messenger ribonucleic acid levels in rat osteoblast-like cells. Mol Endocrinol 3:97–104PubMedCrossRefGoogle Scholar
  34. 34.
    Chang PL, Prince CW (1993) la, 25-dihydroxyvitamin D3 enhances 12-O-tetradecanoylphorbol-13-acetate-induced tumorigenic transformation and osteopontin expression in mouse JB6 epidermal cells. Cancer Res 53:2217–2220PubMedGoogle Scholar
  35. 35.
    Chen TL, Mallory JB, 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. doi:10.1007/BF02556380 PubMedCrossRefGoogle Scholar
  36. 36.
    Scharla SH, Strong DD, Mohan S et al (1991) 1,25-Dihydroxyvitamin D3 differentially regulates the production of insulin-like growth factor I (IGF-I) and IGF-binding protein-4 in mouse osteoblasts. Endocrinology 129:3139–3146PubMedGoogle Scholar
  37. 37.
    Rao LG, Wylie JN (1993) Modulation of parathyroid hormone-sensitive adenylate cyclase in ROS 17/2. 8 cells by dexamethasone 1,25-dihydroxyvitamin D3 and protein kinase C. Bone Miner 23:35–47. doi:10.1016/S0169-6009(08)80089-X PubMedCrossRefGoogle Scholar
  38. 38.
    Rao LG, Murray TM, Wylie JN et al (2005) Long-term culture in dexamethasone unmasks an abnormal phenotype in osteoblasts isolated from osteoporotic subjects. J Endocrinol Invest 28:919–927PubMedGoogle Scholar
  39. 39.
    Neidlinger-Wilke C, Stalla I, Claes L (1995) Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF beta-release in response to cyclic strain. J Biomech 28:1411–1418. doi:10.1016/0021-9290(95)00089-5 PubMedCrossRefGoogle Scholar
  40. 40.
    Torricelli P, Fini M, Giavaresi G (2002) Human osteoblast cultures from osteoporotic and healthy bone: biochemical markers and cytokine expression in basal conditions and in response to 1,25(OH)2D3. Artif Cells Blood Substit Immobil Biotechnol 30:219–227. doi:10.1081/BIO-120004341 PubMedCrossRefGoogle Scholar
  41. 41.
    Bertolini DR, Nedwin GE, Bringman TS (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature 319:516–518. doi:10.1038/319516a0 PubMedCrossRefGoogle Scholar
  42. 42.
    Garrett IR, Durie BGM, Nedwin GE et al (1987) Production of lymphotoxin, a bone resorpting cytokine, by cultured human myeloma cells. N Engl J Med 371:526–532Google Scholar
  43. 43.
    Tashjian AH, Voelkel EF, Lazzaro M (1987) Tumor necrosis factor-α (cathectin) stimulates bone resorption in mouse calvaria via a prostaglandin-mediated mechanism. Endocrinology 120:2029–2036PubMedCrossRefGoogle Scholar
  44. 44.
    Marie PJ, Hott M, Launay JM (1993) In vitro production of cytokines by bone surface derived osteoblastic cells in normal and osteoporotic post-menopausal women; relationship with cell proliferation. J Clin Endocrinol 77:824–830. doi:10.1210/jc.77.3.824 CrossRefGoogle Scholar
  45. 45.
    Ralston S (1994) Analysis of gene expression in human bone biopsies by polymerase chain reaction: evidence for enhanced cytokine expression in postmenopausal osteoporosis. J Bone Miner Res 9:883–890PubMedCrossRefGoogle Scholar
  46. 46.
    Zheng SX, Vrindts Y, De Groote D et al (1997) Increase in cytokine production (IL-1 beta, IL-6, TNF-α, but not INF-gamma, GM-CSF or LIF) by stimulated whole blood cells in postmenopausal osteoporosis. Maturitas 26:63–71. doi:10.1016/S0378-5122(96)01080-8 PubMedCrossRefGoogle Scholar
  47. 47.
    Walsh CA, Birch MA, Fraser WD et al (2000) Cytokine expression by cultured osteoblastas from patients with osteoporotic fractures. Int J Exp Pathol 81:159–163. doi:10.1046/j.1365-2613.2000.00147.x PubMedCrossRefGoogle Scholar
  48. 48.
    Perrini S, Natalicchio A, Laviola L et al (2008) Abnormalities of IGF-I signaling and impaired cell proliferation in osteoblasts from subjects with osteoporosis. Endocrinology 149:1302–1313. doi:10.1210/en.2007-1349 PubMedCrossRefGoogle Scholar
  49. 49.
    Lian JB, Stein GS, Aubin JE (2003) Bone formation: maturation and function activities of osteoblasts linage cells. In: Primer on the metabolic bone diseases and disorders of mineral metabolism, 5th edn. ASBMR, Washington, DC, pp 13–28Google Scholar
  50. 50.
    Vanderschueren D, Gevers G, Raymaekers G (1990) Sex and age-related changes in bone and serum osteocalcin. Calcif Tissue Int 46:179–182. doi:10.1007/BF02555041 PubMedCrossRefGoogle Scholar
  51. 51.
    Westacott CI, Webb GR, Warnok MG (1997) Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum 40:1282–1291PubMedGoogle Scholar
  52. 52.
    Yasumizu T, Okuno T, Fukada Y et al (2000) Age-related changes in bone mineral density and serum-bone-related proteins in premenopausal and postmenopausal Japanese women. Endocr J 47:103–109. doi:10.1507/endocrj.47.103 PubMedCrossRefGoogle Scholar
  53. 53.
    Cantorna MT, Mahon BD (2004) Mounting evidence for Vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med 229:1136–1142Google Scholar
  54. 54.
    Lips P (2004) Which circulating level of 25-hydroxyvitamin D is appropriate? J Steroid Biochem Mol Biol 89–90:611–614. doi:10.1016/j.jsbmb.2004.03.040 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • N. Maruotti
    • 1
  • A. Corrado
    • 1
  • M. Grano
    • 2
  • S. Colucci
    • 2
  • F. P. Cantatore
    • 1
  1. 1.Departement of RheumatologyUniversity of Foggia Medical SchoolFoggiaItaly
  2. 2.Department of Human Anatomy and HistologyUniversity of BariBariItaly

Personalised recommendations