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Biological Trace Element Research

, Volume 173, Issue 2, pp 306–315 | Cite as

Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway

  • Meng Dong
  • Guangjun Jiao
  • Haichun Liu
  • Wenliang Wu
  • Shangzhi Li
  • Qingshi Wang
  • Daxia Xu
  • Xiaofeng Li
  • Huan Liu
  • Yunzhen Chen
Article

Abstract

Silicon is essential for bone formation. A low-silicon diet leads to bone defects, and numerous animal models have demonstrated that silicon supplementation increases bone mineral density (BMD) and reduces bone fragility. However, the exact mechanism of this action has not been characterized. In this study, we aimed to determine the role of biological silicon in the induction of osteoblast differentiation and the possible underlying mechanism. We examined whether orthosilicic acid promotes collagen type 1 (COL-1) and osteocalcin synthesis through the bone morphogenetic protein-2 (BMP-2)/Smad1/5/runt-related transcription factor 2 (RUNX2) signaling pathway by investigating its effect in vitro at several concentrations on COL-1 and osteocalcin synthesis in human osteosarcoma cell lines (MG-63 and U2-OS). The expression of relevant proteins was detected by Western blotting following exposure to noggin, an inhibitor of BMP-2. In MG-63 cells, immunofluorescence methods were applied to detect changes in the expression of BMP-2, phosphorylated Smad1/5 (P-Smad1/5), and RUNX2. Furthermore, rat bone mesenchymal stem cells (BMSCs) were used to determine the effect of orthosilicic acid on osteogenic differentiation. Exposure to 10 μM orthosilicic acid markedly increased the expression of BMP-2, P-Smad1/5, RUNX2, COL-1, and osteocalcin in osteosarcoma cell lines. Enhanced ALP activity and the formation of mineralized nodules were also observed under these conditions. Furthermore, preconditioning with noggin inhibited the silicon-induced upregulation of P-Smad1/5, RUNX2, and COL-1 expression. In conclusion, the BMP-2/Smad1/5/RUNX2 signaling pathway participates in the silicon-mediated induction of COL-1 and osteocalcin synthesis, and orthosilicic acid promotes the osteogenic differentiation of rat BMSCs.

Keywords

Orthosilicic acid Bone morphogenetic protein-2 (BMP-2) Phosphorylated Smad1/5 (P-Smad1/5) Smad1/5 Runt-related transcription factor 2 (RUNX2) Osteoporosis 

Notes

Acknowledgments

This study was supported by a grant from the Department of Science and Technology of Shandong Province (2014GSF118097).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

References

  1. 1.
    Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367:2010–2018CrossRefPubMedGoogle Scholar
  2. 2.
    Carlisle EM (1981) Silicon: a requirement in bone formation independent of vitamin D1. Calcif Tissue Int 33:27–34CrossRefPubMedGoogle Scholar
  3. 3.
    Sahin K, Onderci M, Sahin N, Balci TA, Gursu MF, Juturu V, Kucuk O (2006) Dietary arginine silicate inositol complex improves bone mineralization in quail. Poult Sci 85:486–492CrossRefPubMedGoogle Scholar
  4. 4.
    Merkley JW, Miller ER (1983) The effect of sodium fluoride and sodium silicate on growth and bone strength of broilers. Poult Sci 62:798–804CrossRefPubMedGoogle Scholar
  5. 5.
    Bae YJ, Kim JY, Choi MK, Chung YS, Kim MH (2008) Short-term administration of water-soluble silicon improves mineral density of the femur and tibia in ovariectomized rats. Biol Trace Elem Res 124:157–163CrossRefPubMedGoogle Scholar
  6. 6.
    Kim MH, Bae YJ, Choi MK, Chung YS (2009) Silicon supplementation improves the bone mineral density of calcium-deficient ovariectomized rats by reducing bone resorption. Biol Trace Elem Res 128:239–247CrossRefPubMedGoogle Scholar
  7. 7.
    Casey TR, Bamforth CW (2010) Silicon in beer and brewing. J Sci Food Agric 90:784–788PubMedGoogle Scholar
  8. 8.
    Tucker KL, Jugdaohsingh R, Powell JJ, Qiao N, Hannan MT, Sripanyakorn S, Cupples LA, Kiel DP (2009) Effects of beer, wine, and liquor intakes on bone mineral density in older men and women. Am J Clin Nutr 89:1188–1196CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Seaborn CD, Nielsen FH (1994) Effects of germanium and silicon on bone mineralization. Biol Trace Elem Res 42:151–164CrossRefPubMedGoogle Scholar
  10. 10.
    Seaborn CD, Nielsen FH (2002) Silicon deprivation decreases collagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver. Biol Trace Elem Res 89:251–261CrossRefPubMedGoogle Scholar
  11. 11.
    Seaborn CD, Nielsen FH (2002) Dietary silicon and arginine affect mineral element composition of rat femur and vertebra. Biol Trace Elem Res 89:239–250CrossRefPubMedGoogle Scholar
  12. 12.
    Carlisle EM (1970) Silicon: a possible factor in bone calcification. Science 167:279–280CrossRefPubMedGoogle Scholar
  13. 13.
    Spector TD, Calomme MR, Anderson SH, Clement G, Bevan L, Demeester N, Swaminathan R, Jugdaohsingh R, Berghe DA, Powell JJ (2008) Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. BMC Musculoskelet Disord 9:85CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Calomme M, Geusens P, Demeester N, Behets GJ, D'Haese P, Sindambiwe JB, Van Hoof V, Vanden Berghe D (2006) Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid. Calcif Tissue Int 78:227–232CrossRefPubMedGoogle Scholar
  15. 15.
    Nielsen BDPG, Morris EL, Odom TW, Senor DM, Reynolds JA, Smith WB, Martin MT, Bird EH (1993) Training distance to failure in young racing quarter horses fed sodium zeolite A. J Equine Vet Sci 13:562–567CrossRefGoogle Scholar
  16. 16.
    Lang KJ, Nielsen BD, Waite KL, Hill GM, Orth MW (2001) Supplemental silicon increases plasma and milk silicon concentrations in horses. J Anim Sci 79:2627–2633CrossRefPubMedGoogle Scholar
  17. 17.
    Eisinger J, Clairet D (1993) Effects of silicon, fluoride, etidronate and magnesium on bone mineral density: a retrospective study. Magnes Res 6:247–249PubMedGoogle Scholar
  18. 18.
    Schiano A, Eisinger F, Detolle P, Laponche AM, Brisou B, Eisinger J (1979) Silicon, bone tissue and immunity. Rev Rhum Mal Osteoartic 46:483–486PubMedGoogle Scholar
  19. 19.
    Reffitt DM, Ogston N, Jugdaohsingh R, Cheung HF, Evans BA, Thompson RP, Powell JJ, Hampson GN (2003) Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. Bone 32:127–135CrossRefPubMedGoogle Scholar
  20. 20.
    Jeon EJ, Lee KY, Choi NS, et al. (2006) Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem 281:16502–16511CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang X, Aubin JE, Inman RD (2003) Molecular and cellular biology of new bone formation: insights into the ankylosis of ankylosing spondylitis. Curr Opin Rheumatol 15:387–393CrossRefPubMedGoogle Scholar
  22. 22.
    Zheng H, Guo Z, Ma Q, Jia H, Dang G (2004) Cbfa1/osf2 transduced bone marrow stromal cells facilitate bone formation in vitro and in vivo. Calcif Tissue Int 74:194–203CrossRefPubMedGoogle Scholar
  23. 23.
    Chen D, Zhao M, Mundy GR (2004) Bone morphogenetic proteins. Growth Factors 22:233–241CrossRefPubMedGoogle Scholar
  24. 24.
    Wang X, Harris RE, Bayston LJ, Ashe HL (2008) Type IV collagens regulate BMP signalling in Drosophila. Nature 455:72–77CrossRefPubMedGoogle Scholar
  25. 25.
    Hardwick JC, Kodach LL, Offerhaus GJ, van den Brink GR (2008) Bone morphogenetic protein signalling in colorectal cancer. Nat Rev Cancer 8:806–812CrossRefPubMedGoogle Scholar
  26. 26.
    Franceschi RT, Young J (1990) Regulation of alkaline phosphatase by 1,25-dihydroxyvitamin D3 and ascorbic acid in bone-derived cells. J Bone Miner Res 5:1157–1167CrossRefPubMedGoogle Scholar
  27. 27.
    Lajeunesse D, Frondoza C, Schoffield B, Sacktor B (1990) Osteocalcin secretion by the human osteosarcoma cell line MG-63. J Bone Miner Res 5:915–922CrossRefPubMedGoogle Scholar
  28. 28.
    Orimo H, Goseki-Sone M, Hosoi T, Shimada T (2008) Functional assay of the mutant tissue-nonspecific alkaline phosphatase gene using U2OS osteoblast-like cells. Mol Genet Metab 94:375–381CrossRefPubMedGoogle Scholar
  29. 29.
    Ryu B, Li Y, Qian ZJ, Kim MM, Kim SK (2009) Differentiation of human osteosarcoma cells by isolated phlorotannins is subtly linked to COX-2, iNOS, MMPs, and MAPK signaling: implication for chronic articular disease. Chem Biol Interact 179:192–201CrossRefPubMedGoogle Scholar
  30. 30.
    Body JJ, Bergmann P, Boonen S, et al. (2011) Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club. Osteoporos Int 22:2769–2788CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Office of the Surgeon G (2004) Reports of the Surgeon General. Bone Health and Osteoporosis: A Report of the Surgeon General. Office of the Surgeon General (US), Rockville (MD)Google Scholar
  32. 32.
    Sripanyakorn S, Jugdaohsingh R, Dissayabutr W, Anderson SH, Thompson RP, Powell JJ (2009) The comparative absorption of silicon from different foods and food supplements. Br J Nutr 102:825–834CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Jugdaohsingh R (2007) Silicon and bone health. J Nutr Health Aging 11:99–110PubMedPubMedCentralGoogle Scholar
  34. 34.
    Anasuya A, Bapurao S, Paranjape PK (1996) Fluoride and silicon intake in normal and endemic fluorotic areas. J Trace Elem Med Biol 10:149–155CrossRefPubMedGoogle Scholar
  35. 35.
    Chen F, Cole P, Wen L, Mi Z, Trapido EJ (1994) Estimates of trace element intakes in Chinese farmers. J Nutr 124:196–201PubMedGoogle Scholar
  36. 36.
    Carlisle EM (1976) In vivo requirement for silicon in articular cartilage and connective tissue formation in the chick. J Nutr 106:478–484PubMedGoogle Scholar
  37. 37.
    Schwarz K (1973) A bound form of silicon in glycosaminoglycans and polyuronides. Proc Natl Acad Sci U S A 70:1608–1612CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Panchision DM, Pickel JM, Studer L, Lee SH, Turner PA, Hazel TG, McKay RD (2001) Sequential actions of BMP receptors control neural precursor cell production and fate. Genes Dev 15:2094–2110CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Krause C, Guzman A, Knaus P (2011) Noggin. Int J Biochem Cell Biol 43:478–481CrossRefPubMedGoogle Scholar
  40. 40.
    Smith WC, Harland RM (1992) Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Cell 70:829–840CrossRefPubMedGoogle Scholar
  41. 41.
    Groppe J, Greenwald J, Wiater E, et al. (2003) Structural basis of BMP signaling inhibition by noggin, a novel twelve-membered cystine knot protein. J Bone Joint Surg Am 85-A(Suppl 3):52–58PubMedGoogle Scholar
  42. 42.
    Kayongo-Male H, Julson JL (2008) Effects of high levels of dietary silicon on bone development of growing rats and turkeys fed semi-purified diets. Biol Trace Elem Res 123:191–201CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Meng Dong
    • 1
  • Guangjun Jiao
    • 1
  • Haichun Liu
    • 1
  • Wenliang Wu
    • 1
  • Shangzhi Li
    • 1
  • Qingshi Wang
    • 1
  • Daxia Xu
    • 1
  • Xiaofeng Li
    • 1
  • Huan Liu
    • 1
  • Yunzhen Chen
    • 1
  1. 1.Department of OrthopedicsQilu Hospital of Shandong UniversityJi’nanChina

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