Biosilica-Based Strategies for Treatment of Osteoporosis and Other Bone Diseases

  • Heinz C. SchröderEmail author
  • Matthias Wiens
  • Xiaohong Wang
  • Ute Schloßmacher
  • Werner E. G. MüllerEmail author
Part of the Progress in Molecular and Subcellular Biology book series (PMSB, volume 52)


Osteoporosis is a common disease in later life, which has become a growing public health problem. This degenerative bone disease primarily affects postmenopausal women, but also men may suffer from reduced bone mineral density. The development of prophylactic treatments and medications of osteoporosis has become an urgent issue due to the increasing proportion of the elderly in the population. Apart from medical/hormonal treatments, current strategies for prophylaxis of osteoporosis are primarily based on calcium supplementation as a main constituent of bone hydroxyapatite mineral. Despite previous reports suggesting an essential role in skeletal growth and development, the significance of the trace element silicon in human bone formation has attracted major scientific interest only rather recently. The interest in silicon has been further increased by the latest discoveries in the field of biosilicification, the formation of the inorganic silica skeleton of the oldest still extant animals on Earth, the sponges, which revealed new insights in the biological function of this element. Sponges make use of silicon to build up their inorganic skeleton which consists of biogenously formed polymeric silica (biosilica). The formation of biosilica is mediated by specific enzymes, silicateins, which have been isolated, characterized, and expressed in a recombinant way. Epidemiological studies revealed that dietary silicon reduces the risk of osteoporosis and other bone diseases. Recent results allowed for the first time to understand the molecular mechanism underlying the protective effect of silicic acid/biosilica against osteoporosis. Biosilica was shown to modulate the ratio of expression of two cytokines involved in bone formation–RANKL and osteoprotegerin. Hence, biosilica has been proposed to have a potential in prophylaxis and therapy of osteoporosis and related bone diseases.


Bone Mineral Density Silicic Acid Strontium Ranelate Siliceous Sponge Tumor Necrosis Factor Receptor Superfamily 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by grants from the Bundesministerium für Bildung und Forschung (project “Center of Excellence BIOTECmarin”), the Deutsche Forschungsgemeinschaft (Schr 277/10-1), the European Commission (no PITN-GA-2008-215507 – BIOMINTEC), the BiomaTiCS consortium of the Mainz University Medical Center, the Johannes Gutenberg University Research Center for Complex Matter (COMATT), and the International S & T Cooperation Program of China (Grant No. 2008DFA00980). W.E.G.M. is a holder of an ERC Advanced Grant (no 268476 BIOSILICA).


  1. Adachi JD (1997) Corticosteroid-induced osteoporosis. Am J Med Sci 313:41–49PubMedGoogle Scholar
  2. Adler AJ, Berlyne GM (1986) Silicon metabolism II. Renal handling chronic renal failure patients. Nephron 44:36–39PubMedGoogle Scholar
  3. Adler AJ, Etzion Z, Berlyne GM (1986) Uptake, distribution, and excretion of 31silicon in normal rats. Am J Physiol 251:E670–E673PubMedGoogle Scholar
  4. Adkisson HD, Strauss-Schoenberger J, Gillis M, Wilkins R, Jackson M, Hruska KA (2000) Rapid quantitative bioassay of osteoinduction. J Orthop Res 18:503–511PubMedGoogle Scholar
  5. Albrektsson T, Johansson C (2001) Osteoinduction, osteoconduction and osseointegration. Eur Spine J 10:S96–S101PubMedGoogle Scholar
  6. Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19:2012–2020PubMedGoogle Scholar
  7. Arumugam MQ, Ireland DC, Brooks RA, Rushton N, Bonfield W (2006) The effect of orthosilicic acid on collagen type I, alkaline phosphatase and osteocalcin mRNA expression in human bone-derived osteoblasts in vitro. Key Eng Mater 32:309–311Google Scholar
  8. Berlyne GM, Adler AJ, Ferran N, Bennett S, Holt J (1986) Silicon metabolism I: some aspects of renal silicon handling in normal man. Nephron 43:5–9PubMedGoogle Scholar
  9. Bhattacharyya P, Vulcani BE (1980) Sodium-dependent silicate transport in the apochlorotic marine diatom. Proc Natl Acad Sci USA 77:6386–6390PubMedGoogle Scholar
  10. Bhattacharjee H, Mukhopadhyay R, Thiyagarajan S, Rosen BP (2008) Aquaglyceroporins: ancient channels for metalloids. J Biol 7:33PubMedGoogle Scholar
  11. Blick SK, Dhillon S, Keam SJ (2009) Spotlight on teriparatide in osteoporosis. BioDrugs 23:197–199PubMedGoogle Scholar
  12. Borsje MA, Ren Y, de Haan-Visser HW, Kuijer R (2010) Comparison of low-intensity pulsed ultrasound and pulsed electromagnetic field treatments on OPG and RANKL expression in human osteoblast-like cells. Angle Orthod 80:498–503PubMedGoogle Scholar
  13. Brady MC, Dobson PRM, Thavarajah M, Kanis JA (1991) Zeolite A stimulates proliferation and protein synthesis in human osteoblast-like cells and osteosarcoma cell line MG-63. J Bone Miner Res 6:S139Google Scholar
  14. Bretcanu O, Misra S, Roy I, Renghini C, Fiori F, Boccaccini AR, Salih V (2009) In vitro biocompatibility of 45 S5 Bioglass®-derived glass–ceramic scaffolds coated with poly(3-hydroxybutyrate). J Tissue Eng Regen Med 3:139–148PubMedGoogle Scholar
  15. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268PubMedGoogle Scholar
  16. Calomme MR, Van den Berghe DA (1997) Supplementation of calves with stabilized orthosilicic acid. Effect on the Si, Ca, Mg, and P concentrations in serum and the collagen concentration in skin and cartilage. Biol Trace Elem Res 56:153–165PubMedGoogle Scholar
  17. Calomme M, Geusens P, Demeester N, Behets GJ, D'Haese P, Sindambiwe JB, Van Hoof V, Van den Berghe D (2006) Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid. Calcif Tissue Int 78:227–232PubMedGoogle Scholar
  18. Calvo E, Castañeda S, Largo R, Fernández-Valle ME, Rodríguez-Salvanés F, Herrero-Beaumont G (2007) Osteoporosis increases the severity of cartilage damage in an experimental model of osteoarthritis in rabbits. Osteoarthr Cartil 15:69–77PubMedGoogle Scholar
  19. Canalis E (2010) New treatment modalities in osteoporosis. Endocr Pract 29:1–23Google Scholar
  20. Carlisle EM (1972) Silicon: an essential element for the chick. Science 178:619–621PubMedGoogle Scholar
  21. Carlisle EM (1976) In vivo requirement for silicon in articular cartilage and connective tissue formation in the chick. J Nutr 106:478–484PubMedGoogle Scholar
  22. Carlisle EM (1981) Silicon in bone formation, vol 4. In: Simpson TL, Volcani BE (eds) Springer Verlag, New York, pp 69–94Google Scholar
  23. Carlisle EM (1986) Silicon as an essential trace element in animal nutrition. In: Ciba Foundation symposium 121. Wiley, Chichester, UK, pp 123–139Google Scholar
  24. Carlisle EM, Alpenfels WF (1980) A silicon requirement for normal growth for cartilage in culture. Fed Proc 39:787Google Scholar
  25. Carlisle EM, Alpenfels WF (1984) The role of silicon in proline synthesis. Fed Proc 43:680Google Scholar
  26. Carlisle EM, Garvey DL (1982) The effect of silicon on formation of extracellular matrix components by chondrocytes in culture. Fed Proc 41:461Google Scholar
  27. Carlisle EM, Berger JW, Alpenfels WF (1981) A silicon requirement for prolyl hydroxylase activity. Fed Proc 40:886Google Scholar
  28. Carlisle EM, Suchil C (1983) Silicon and ascorbate interaction in cartilage formation in culture. Fed Proc 42:398Google Scholar
  29. Cha JN, Shimizu K, Zhou Y, Christianssen SC, Chmelka BF, Stucky GD, Morse DE (1999) Silicatein filaments and subunits from a marine sponge direct the polymerization of silica and silicones in vitro. Proc Natl Acad Sci USA 96:361–365PubMedGoogle Scholar
  30. Chen H, Clarkson BH, Sun K, Mansfield JF (2005) Self-assembly of synthetic hydroxyapatite nanorods into an enamel prism-like structure. J Colloid Interface Sci 288:97–103PubMedGoogle Scholar
  31. Chen QZ, Thompson ID, Boccaccini AR (2006) 45 S5 Bioglass®-derived glass-ceramic scaffolds for bone tissue engineering. Biomaterials 27:2414–2425PubMedGoogle Scholar
  32. Collin-Osdoby P (2004) Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res 95:1046–1057PubMedGoogle Scholar
  33. Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767PubMedGoogle Scholar
  34. D'Haese PC, Shaheen FA, Huraid SO, Djukanovic L, Polenakovic MH, Spasovski G, Shikole A, Schurgers ML, Daneels RF, Lamberts LV, Van Landeghem GF, De Broe ME (1995) Increased silicon levels in dialysis patients due to high silicon content in the drinking water, inadequate water treatment procedures, and concentrate contamination: a multicentre study. Nephrol Dial Transplant 10:1838–1844PubMedGoogle Scholar
  35. EFSA (2009) Choline-stabilised orthosilicic acid added for nutritional purposes to food supplements scientific opinion of the panel on food additives and nutrient sources added to food. The EFSA J 948:1–23Google Scholar
  36. Eglin D, Shafran KL, Livage J, Coradin T, Perry CC (2006) Comparative study of the influence of several silica precursors on collagen self-assembly and of collagen on ‘Si’ speciation and condensation. J Mater Chem 16:4220–4230Google Scholar
  37. Eliseev RA, Schwarz EM, Zuscik MJ, O’Keefe Regis J, Drissi H, Rosier RN (2006) Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NFκnB. Exp Cell Res 312:40–50PubMedGoogle Scholar
  38. Faibish D, Ott SM, Boskey AL (2006) Mineral changes in osteoporosis: a review. Clin Orthop Relat Res 443:28–38PubMedGoogle Scholar
  39. Fromigue O, Hay E, Modrowski D, Bouvet S, Jacquel A, Auberge P, Marie PJ (2006) RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42/p44-MAPKs-Bcl-2 signaling independently of BMP-2 and cell differentiation. Cell Death Differ 13:1845–1856PubMedGoogle Scholar
  40. Gallagher JC (2008) Advances in bone biology and new treatments for bone loss. Maturitas 60:65–69PubMedGoogle Scholar
  41. Gao T, Aro HT, Ylänen H, Vuorio E (2001) Silica-based bioactive glasses modulate expression of bone morphogenetic protein-2 mRNA in Saos-2 osteoblasts in vitro. Biomaterials 22:1475–1483PubMedGoogle Scholar
  42. Gao BB, Clermont A, Rook S, Fonda SJ, Srinivasan VJ, Wojtkowski M, Fujimoto JG, Avery RL, Arrigg PG, Bursell SE, Aiello LP, Feener E (2007) Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat Med 13:181–188PubMedGoogle Scholar
  43. Gardner MJ, Demetrakopoulos D, Shindle MK, Griffith MH, Lane JM (2006) Osteoporosis and skeletal fractures. HSS J 2:62–69PubMedGoogle Scholar
  44. Glantz PO (1987) Comment. In: Williams DF (ed) Progress in biomedical engineering, vol 4. definitions in biomaterials. Elsevier, Amsterdam, p 24Google Scholar
  45. Gröger C, Sumper M, Brunner E (2007) Silicon uptake and metabolism of the marine diatom Thalassiosira pseudonana: solid-state 29Si NMR and fluorescence microscopic studies. J Struct Biol 161:55–63PubMedGoogle Scholar
  46. Hausser HJ, Brenner RE (2005) Phenotypic instability of SaOS-2 cells in long-term culture. Biochem Biophys Res Commun 333:216–222PubMedGoogle Scholar
  47. Hay E, Lemonnier J, Fromigue O, Guenou H, Pierre JM (2004) Bone morphogenetic protein receptor IB signaling mediates apoptosis independently of differentiation in osteoblastic cells. J Biol Chem 279:1650–1658PubMedGoogle Scholar
  48. Hayman AR, Jones SJ, Boyde A, Foster D, Colledge WH, Carlton MB, Evans MJ, Cox TM (1996) Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis. Development 122:3151–3162PubMedGoogle Scholar
  49. Hench LL (1998) Bioceramics. J Am Ceram Soc 81:1705–1728Google Scholar
  50. Hench LL (2006) The story of bioglass. J Mater Sci Mater Med 17:967–978PubMedGoogle Scholar
  51. Hench LL, Paschall HA (1973) Direct chemical bond of bioactive glass-ceramic materials to bone and muscle. J Biomed Mater Res 4:25–42Google Scholar
  52. Hench LL, Wilson J (1984) Surface-active biomaterials. Science 226:630–636PubMedGoogle Scholar
  53. Hench LL, Polak JM (2002) Third-generation biomedical materials. Science 295:1014–1017PubMedGoogle Scholar
  54. Hollberg K, Nordahl J, Hultenby K, Mengarelli-Widholm S, Andersson G, Reinholt FP (2005) Polarization and secretion of cathepsin K precede tartarate-resistant acid phosphatase secretion to the ruffled border area during the activation of matrix-resorbing clasts. J Bone Miner Metab 23:441–449PubMedGoogle Scholar
  55. Hott M, de Pollak C, Modrowski DMPJ (1993) Short-term effects of organic silicon on trabecular bone in mature ovariectomized rats. Calcif Tissue Int 53:174–179PubMedGoogle Scholar
  56. Iler RK (1979) Solubility, polymerisation, colloid and surface properties, and biochemistry. Wiley, New YorkGoogle Scholar
  57. Jin H, Heller DA, Sharma R, Strano MS (2009) Size-dependent cellular uptake and expulsion of single-walled carbon nanotubes: single particle tracking and a generic uptake model for nanoparticles. Nano 3:149–158Google Scholar
  58. Jugdaohsingh R (2007) Silicon and bone health. J Nutr Health Aging 11:99–110PubMedGoogle Scholar
  59. Jugdaohsingh R, Reffitt DM, Oldham C, Day JP, Fifield LK, Thompson RPH, Powell JJ (2000) Oligomeric but not monomeric silica prevents aluminum absorption in humans. Am J Clin Nutr 71:944–949PubMedGoogle Scholar
  60. Jugdaohsingh R, Anderson SH, Tucker KL, Elliott H, Kiel DP, Thompson RPH, Powell JJ (2002) Dietary silicon intake and absorption. Am J Clin Nutr 75:887–893PubMedGoogle Scholar
  61. Jugdaohsingh R, Tucker KL, Qiao N, Cupples LA, Kiel DP, Powell JJ (2004) Silicon intake is a major dietary determinant of bone mineral density in men and pre-menopausal women of the Framingham offspring cohort. J Bone Miner Res 19:297–307PubMedGoogle Scholar
  62. Kaandorp JA, Blom JG, Verhoef J, Filatov M, Postma M, Müller WEG (2008) Modelling genetic regulation of growth and form in a branching sponge. Proc Biol Sci 275:2569–2575PubMedGoogle Scholar
  63. Kaluzhnaya OV, Belikov SI, Schröder HC, Wiens M, Giovine M, Krasko A, Müller IM, Müller WEG (2005) Dynamics of skeleton formation in the Lake Baikal sponge Lubomirskia baicalensis Part II. Molecular biological studies. Naturwissenschaften 92:134–138PubMedGoogle Scholar
  64. Kanamaru F, Iwai H, Ikeda T, Nakajima A, Ishikawa I, Azuma M (2004) Expression of membrane-bound and soluble receptor activator of NF-kappa B ligand (RANKL) in human T cells. Immunol Lett 94:239–246PubMedGoogle Scholar
  65. Katz JM, Nataraj C, Jaw R, Deigl E, Bursac P (2008) Demineralized bone matrix as an osteoinductive biomaterial and in vitro predictors of its biological potential. J Biomed Mater Res 89B:127–134Google Scholar
  66. Kelly SE, Di Benedetto A, Greco A, Howard CM, Sollars VE, Primerano DA, Valluri JV, Claudio PP (2010) Rapid selection and proliferation of CD133(+) cells from cancer cell lines: chemotherapeutic implications. PLoS ONE 5:e10035. doi: 10.1371/journal.pone.0010035 PubMedGoogle Scholar
  67. Keeting PE, Oursler MJ, Wiegand KE, Bonde SK, Spelsberg TC, Riggs BL (1992) Zeolite-A increases proliferation, differentiation, and transforming growth-factor-b production in normal adult human osteoblast-like cells-in vitro. J Bone Miner Res 7:1281–1289PubMedGoogle Scholar
  68. Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142:5050–5055PubMedGoogle Scholar
  69. Khosla S, Amin S, Orwoll E (2008a) Osteoporosis in men. Endocr Rev 29:441–464PubMedGoogle Scholar
  70. Khosla S, Westendorf JJ, Oursler MJ (2008b) Building bone to reverse osteoporosis and repair fractures. J Clin Invest 118:421–428PubMedGoogle Scholar
  71. Kim M-H, Bae Y-J, Choi M-K, Chung Y-S (2009) Silicon supplementation improves the bone mineral density of calcium-deficient ovariectomized rats by reducing bone resorption. Biol Trace Elem Res 128:239–247PubMedGoogle Scholar
  72. Krasko A, Batel R, Schröder HC, Müller IM, Müller WEG (2000) Expression of silicatein and collagen genes in the marine sponge Suberites domuncula is controlled by silicate and myotrophin. Eur J Biochem 267:4878–4887PubMedGoogle Scholar
  73. Lane NE, Yao W (2009) Developments in the scientific understanding of osteoporosis. Arthritis Res Ther 11:228PubMedGoogle Scholar
  74. Leibbrandt A, Penninger JM (2008) RANK/RANKL: regulators of immune responses and bone physiology. Ann NY Acad Sci 1143:123–150PubMedGoogle Scholar
  75. Le Pennec G, Perovic S, Ammar SMA, Grebenjuk VA, Steffen R, Brümmer F, Müller WEG (2003) Cultivation of primmorphs from the marine sponge Suberites domuncula : morphogenetic potential of silicon and iron. A review J Biotechnol 100:93–108Google Scholar
  76. Leyhausen G, Lorenz B, Zhu H, Geurtsen W, Bohnensack R, Müller WEG, Schröder HC (1998) Inorganic polyphosphate in human osteoblast-like cells. J Bone Miner Res 13:803–812PubMedGoogle Scholar
  77. Li Q, Kannan A, Wang W, Demayo FJ, Taylor RN, Bagchi MK, Bagchi IC (2007) Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. J Biol Chem 282:31725–31732PubMedGoogle Scholar
  78. López-Alvarez M, Solla EL, González P, Serra J, León B, Marques AP, Reis RL (2009) Silicon-hydroxyapatite bioactive coatings (Si-HA) from diatomaceous earth and silica. Study of adhesion and proliferation of osteoblast-like cells. J Mater Sci Mater Med 20:1131–1136PubMedGoogle Scholar
  79. Lorenz B, Schröder HC (2001) Mammalian intestinal alkaline phosphatase acts as highly active exopolyphosphatase. Biochim Biophys Acta 1547:254–261PubMedGoogle Scholar
  80. MacDonald HM, Hardcastle AE, Jugdaohsingh R, Reid DM, Powell JJ (2005) Dietary silicon intake is associated with bone mineral density in premenopasual women and postmenopausal women taking HRT. J Bone Miner Res 20:S393Google Scholar
  81. Maehira F, Iinuma Y, Eguchi Y, Miyagi I, Teruya S (2008) Effects of soluble silicon compound and deep-sea water on biochemical and mechanical properties of bone and the related gene expression in mice. J Bone Miner Metab 26:446–455PubMedGoogle Scholar
  82. Maehira F, Miyagi I, Eguchi Y (2009) Effects of calcium sources and soluble silicate on bone metabolism and the related gene expression in mice. Nutrition 25:581–589PubMedGoogle Scholar
  83. Mann S (2001) Biomineralization: principles and concepts in bioinorganic materials chemistry. Oxford University Press, OxfordGoogle Scholar
  84. McNaughton SA, Bolton-Smith C, Mishra GD, Jugdaohsingh R, Powell JJ (2005) Dietary silicon intake in post-menopausal women. Br J Nutr 94:813–817PubMedGoogle Scholar
  85. Matsuzaki K, Katayama K, Takahashi Y, Nakamura I, Udagawa N, Tsurukai T, Nishinakamura R, Toyama Y, Yabe Y, Hori M, Takahashi N, Suda T (1999) Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene. Endocrinology 140:925–932PubMedGoogle Scholar
  86. Morgan EF, Barnes GL, Einhorn TA (2008) The bone organ system: form and function. In: Marcus R, Feldman D, Nelson DA, Rosen CJ (eds) Osteoporosis., 3rd edn. Elsevier, San Diego, pp 3–25Google Scholar
  87. Mori K, Berreur M, Blanchard F, Chevalier C, Guisle-Marsollier I, Masson M, Rédini F, Heymann D (2007) Receptor activator of nuclear factor-κB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells. Oncol Rep 18:1365–1371PubMedGoogle Scholar
  88. Morse DE (1999) Silicon biotechnology: harnessing biological silica production to construct new materials. Trends Biotechnol 17:230–232Google Scholar
  89. Müller WEG (2003) Silicon biomineralization: biology-biochemistry-molecular biology-biotechnology. Springer, BerlinGoogle Scholar
  90. Müller WEG, Rothenberger M, Boreiko A, Tremel W, Reiber A, Schröder HC (2005) Formation of siliceous spicules in the marine demosponge Suberites domuncula. Cell Tissue Res 321:285–297PubMedGoogle Scholar
  91. Müller WE, Belikov SI, Tremel W, Perry CC, Gieskes WW, Boreiko A, Schröder HC (2006) Siliceous spicules in marine demosponges (example Suberites domuncula ). Micron 37:107–120PubMedGoogle Scholar
  92. Müller WEG, Boreiko A, Wang XH, Krasko A, Geurtsen W, Custódio MR, Winkler T, Lukić-Bilela L, Link T, Schröder HC (2007a) Morphogenetic activity of silica and bio-silica on the expression of genes, controlling biomineralization using SaOS-2 cells. Calcif Tissue Int 81:382–393PubMedGoogle Scholar
  93. Müller WEG, Wang XM, Belikov SI, Tremel W, Schloßmacher U, Natoli A, Brandt D, Boreiko A, Tahir MN, Müller IM, Schröder HC (2007b) Formation of siliceous spicules in demosponges: example Suberites domuncula. In: Bäuerlein E (ed) Handbook of biomineralization; Vol. 1: biological aspects and structure formation. Wiley-VCH, Weinheim, pp 59–82Google Scholar
  94. Müller WEG, Jochum K, Stoll B, Wang XH (2008a) Formation of giant spicule from quartz glass by the deep sea sponge Monorhaphis. Chem Mater 20:4703–4711Google Scholar
  95. Müller WEG, Schloßmacher U, Wang XH, Boreiko A, Brandt D, Wolf SE, Tremel W, Schröder HC (2008b) Poly(silicate)-metabolizing silicatein in siliceous spicules and silicasomes of demosponges comprises dual enzymatic activities (silica-polymerase and silica-esterase). FEBS J 275:362–370PubMedGoogle Scholar
  96. Müller WEG, Wang X, Kropf K, Boreiko A, Schloßmacher U, Brandt D, Schröder HC, Wiens M (2008c) Silicatein expression in the hexactinellid Crateromorpha meyeri: the lead marker gene restricted to siliceous sponges. Cell Tissue Res 333:339–351PubMedGoogle Scholar
  97. Müller WEG, Wang X, Burghard Z, Bill J, Krasko A, Boreiko A, Schloßmacher U, Schröder HC, Wiens M (2009a) Bio-sintering processes in hexactinellid sponges: fusion of biosilica in giant basal spicules from Monorhaphis chuni. J Struct Biol 168:548–561PubMedGoogle Scholar
  98. Müller WE, Wang X, Cui FZ, Jochum KP, Tremel W, Bill J, Schröder HC, Natalio F, Schlossmacher U, Wiens M (2009b) Sponge spicules as blueprints for the Biofabrication of inorganic-organic composites and biomaterials. Appl Microbiol Biotechnol 83:397–413PubMedGoogle Scholar
  99. Müller WEG, Wang X, Sinha B, Wiens M, Schröder HC, Jochum KP (2010) NanoSIMS: Insights into the organization of the proteinaceous scaffold within hexactinellid sponge spicules. Chembiochem 11:077–1082Google Scholar
  100. Natalio F, Link T, Müller WEG, Schröder HC, Cui FZ, Wang XH, Wiens M (2010) Bioengineering of the silica-polymerizing enzyme silicatein-α for a targeted application to hydroxyapatite. Acta Biomater 6:3720–3728PubMedGoogle Scholar
  101. Nielsen FH (2008) A novel silicon complex is as effective as sodium metasilicate in enhancing the collagen-induced inflammatory response of silicon-deprived rats. J Trace Elem Med Biol 22:39–49PubMedGoogle Scholar
  102. Oddie GW, Schenk G, Angel NZ, Walsh N, Guddat LW, de Jersey J, Cassady AI, Hamilton SE, Hume DA (2000) Structure, function, and regulation of tartrate-resistant acid phosphatase. Bone 27:575–584PubMedGoogle Scholar
  103. Patlak M (2001) Bone builders: the discoveries behind preventing and treating osteoporosis. FASEB J 15:1677E–EPubMedGoogle Scholar
  104. Perry CC (2003) Silicification: the processes by which organisms capture and mineralize silica. Rev Mineral Geochem 54:291–327Google Scholar
  105. Perry CC, Keeling-Tucker T (2000) Biosilification: the role of the organic matrix in structure control. J Biol Inorg Chem 5:537–550PubMedGoogle Scholar
  106. Perry CC, Belton D, Shafran K (2003) Studies of biosilicas: structural aspects, chemical principles, model studies and the future. In: Müller WEG (ed) Silicon biomineralization: Biology – Biochemistry – Molecular biology – Biotechnology. Prog Mol Subcell Biol 33:269–299Google Scholar
  107. Postiglione L, DiDomenico G, Montagnani S, Di Spigna G, Salzano S, Castaldo C, Ramaglia L, Sbordone L, Rossi G (2003) Granulocyte macrophage colony-stimulating factor (GM-CSF) induces the osteoblastic differentiation of the human osteosarcoma cell line SaOS-2. Calcif Tissue Int 72:85–97PubMedGoogle Scholar
  108. Raisz LG (2005) Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest 115:3318–3325PubMedGoogle Scholar
  109. Reffitt DM, Jugdoahsingh R, Thompson RPH, Powell JJ (1999) Silicic acid: its gastrointestinal uptake and urinary excretion in man and effects on aluminium excretion. J Inorg Biochem 76:141–147PubMedGoogle Scholar
  110. Reffitt DM, Ogston N, Jugdaohsingh R, Cheung HF, Evans BA, Thompson RP, Powell JJ, Hampson GN (2003) Orthosilicic acid stimulates collagen type I synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. Bone 32:127–135PubMedGoogle Scholar
  111. Reginster JY, Burlet N (2006) Osteoporosis: a still increasing prevalence. Bone 38(2 Suppl 1):S4–S9PubMedGoogle Scholar
  112. Reid IR (2008) Anti-resorptive therapies for osteoporosis. Stem Cell Dev Biol 19:473–478Google Scholar
  113. Rodan GA, Martin TJ (1982) Role of osteoblasts in hormonal control of bone resorption - hypothesis [letter]. Calcif Tissue Int 34:311PubMedGoogle Scholar
  114. Russell RG, Croucher PI, Rogers MJ (1999) Bisphosphonates: pharmacology, mechanisms of action and clinical uses. Osteoporos Int 9(Suppl 2):S66–S80PubMedGoogle Scholar
  115. 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 85:486–492PubMedGoogle Scholar
  116. Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367:2010–2018PubMedGoogle Scholar
  117. Sasaki S (2008) Introduction for special issue for aquaporin expanding the world of aquaporins: new members and new functions. Pflügers Arch Eur J Physiol 456:647–649Google Scholar
  118. Schröder HC, Krasko A, Batel R, Skorokhod A, Pahler S, Kruse M, Müller IM, Müller WEG (2000a) Stimulation of protein (collagen) synthesis in sponge cells by a cardiac myotrophin-related molecule from Suberites domuncula. FASEB J 14:2022–2031PubMedGoogle Scholar
  119. Schröder HC, Kurz L, Müller WEG, Lorenz B (2000b) Polyphosphate in bone. Biochemistry (Moscow) 65:296–303Google Scholar
  120. Schröder HC, Krasko A, Le Pennec G, Adell T, Hassanein H, Müller IM, Müller WEG (2003) Silicase, an enzyme which degrades biogenous amorphous silica: Contribution to the metabolism of silica deposition in the demosponge Suberites domuncula. In: Müller WEG (ed) Silicon biomineralization: biology-biochemistry-molecular biology-biotechnology. Springer, Berlin, Prog Mol Subcell Biol 33:249–268Google Scholar
  121. Schröder HC, Perović-Ottstadt S, Rothenberger M, Wiens M, Schwertner H, Batel R, Korzhev M, Müller IM, Müller WEG (2004) Silica transport in the demosponge Suberites domuncula : Fluorescence emission analysis using the PDMPO probe and cloning of a potential transporter. Biochem J 381:665–673PubMedGoogle Scholar
  122. Schröder HC, Borejko A, Krasko A, Reiber A, Schwertner H, Müller WEG (2005a) Mineralization of SaOS-2 cells on enzymatically (Silicatein) modified bioactive osteoblast-stimulating surfaces. J Biomed Mat Res B Appl Biomater 75B:387–392Google Scholar
  123. Schröder HC, Perović-Ottstadt S, Grebenjuk VA, Engel S, Müller IM, Müller WEG (2005b) Biosilica formation in spicules of the sponge Suberites domuncula : Synchronous expression of a gene cluster. Genomics 85:666–678PubMedGoogle Scholar
  124. Schröder HC, Boreiko A, Korzhev M, Tahir MN, Tremel W, Eckert C, Ushijima H, Müller IM, Müller WEG (2006) Co-Expression and functional interaction of silicatein with galectin: matrix-guided formation of siliceous spicules in the marine demosponge Suberites domuncula. J Biol Chem 281:12001–12009PubMedGoogle Scholar
  125. Schröder HC, Brandt D, Schlossmacher U, Wang X, Tahir MN, Tremel W, Belikov SI, Müller WEG (2007a) Enzymatic production of biosilica glass using enzymes from sponges: basic aspects and application in nanobiotechnology (material sciences and medicine). Naturwissenschaften 94:339–359PubMedGoogle Scholar
  126. Schröder HC, Natalio F, Shukoor I, Tremel W, Schloßmacher U, Wang XH, Müller WEG (2007b) Apposition of silica lamellae during growth of spicules in the demosponge Suberites domuncula : biological/biochemical studies and chemical/biomimetical confirmation. J Struct Biol 159:325–334PubMedGoogle Scholar
  127. Schröder HC, Wang XH, Tremel W, Ushijima H, Müller WEG (2008) Biofabrication of biosilica-glass by living organisms. Nat Prod Rep 25:455–474PubMedGoogle Scholar
  128. Schröder HC, Wiens M, Schloßmacher U, Brandt D, Müller WEG (2010) Silicatein-mediated polycondensation of orthosilicic acid: Modeling of catalytic mechanism involving ring formation. Silicon, in press (DOI: 10.1007/s12633-010-9057-4)Google Scholar
  129. Schwarz K (1973) A bound form of silicon in glycosaminoglycans and polyuronides. Proc Natl Acad Sci USA 70:1608–1612PubMedGoogle Scholar
  130. Schwarz K, Milne DB (1972) Growth promoting effects of silicon in rats. Nature 239:333–334PubMedGoogle Scholar
  131. 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 89:251–261PubMedGoogle Scholar
  132. Shimizu K, Cha J, Stucky GD, Morse DE (1998) Silicatein alpha: cathepsin L-like protein in sponge biosilica. Proc Natl Acad Sci USA 95:6234–6238PubMedGoogle Scholar
  133. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMedGoogle Scholar
  134. Singer A, Grauer A (2010) Denosumab for the management of postmenopausal osteoporosis. Postgrad Med 122:176–187PubMedGoogle Scholar
  135. 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 9:85PubMedGoogle Scholar
  136. Sripanyakorn S, Jugdaohsingh R, Elliott H, Walker C, Mehta P, Shoukru S, Thompson RPH, Powell JJ (2004) The silicon content of beer and its bioavailability in healthy volunteers. Brit J Nutr 91:403–409PubMedGoogle Scholar
  137. 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 102:825–834PubMedGoogle Scholar
  138. Stein GS, Lian JB, van Wijnen AJ, Stein JL, Montecino M, Javed A, Zaidi SK, Young DW, Choi J-Y, Pockwinse SM (2004) Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression. Oncogene 23:4315–4329PubMedGoogle Scholar
  139. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357PubMedGoogle Scholar
  140. Tahir MN, Théato P, Müller WEG, Schröder HC, Janshoff A, Zhang J, Huth J, Tremel W (2004) Monitoring the formation of biosilica catalysed by histidin-tagged silicatein. Chem Commun 24:2848–2849Google Scholar
  141. Tanaka H, Nagai E, Murata H, Tsubone T, Shirakura Y, Sugiyama T, Taguchi T, Kawai S (2001) Involvement of bone morphogenic protein-2 (BMP-2) in the pathological ossification process of the spinal ligament. Rheumatology 40:1163–1168PubMedGoogle Scholar
  142. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A (2007) Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 370:657–666PubMedGoogle Scholar
  143. Taranta A, Brama M, Teti A, De luca V, Scandurra R, Spera G, Agnusdei D, Termine JD, Migliaccio S (2002) The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro. Bone 30:368–376PubMedGoogle Scholar
  144. Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289:1504–1508PubMedGoogle Scholar
  145. Thamatrakoln K, Alverson AJ, Hildebrand M (2006) Comparative sequence analysis of diatom silicon transporters: towards a mechanistic model of silicon transport. J Phycol 42:822–834Google Scholar
  146. Wada T, Nakashima T, Hiroshi N, Penninger JM (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12:17–25PubMedGoogle Scholar
  147. Wang JC, Hemavathy K, Charles W, Zhang H, Dua PK, Novetsky AD, Chang T, Wong C, Jabara M (2004) Osteosclerosis in idiopathic myelofibrosis is related to the overproduction of osteoprotegerin (OPG). Exp Hematol 32:905–910PubMedGoogle Scholar
  148. Wang XH, Hu S, Gan L, Wiens M, Müller WEG (2010) Sponges (Porifera) as living metazoan witnesses from the neoproterozoic: biomineralization and the concept of their evolutionary success. Terra Nova 22:1–11Google Scholar
  149. Weiner S, Traub W (1992) Bone structure: from angstroms to microns. FASEB J 6:879–885PubMedGoogle Scholar
  150. Wetzel P, Hasse A, Papadopoulos S, Voipio J, Kaila K, Gros G (2001) Extracellular carbonic anhydrase activity facilitates lactic acid transport in rat skeletal muscle fibres. J Physiol 531:743–756PubMedGoogle Scholar
  151. Wiens M, Belikov SI, Kaluzhnaya OV, Krasko A, Schröder HC, Perovic-Ottstadt S, Müller WEG (2006) Molecular control of serial module formation along the apical-basal axis in the sponge Lubomirskia baicalensis: silicateins, mannose-binding lectin and Mago Nashi. Dev Genes Evol 216:229–242PubMedGoogle Scholar
  152. Wiens M, Bausen M, Natalio F, Link T, Schlossmacher U, Müller WEG (2009) The role of the silicatein-α interactor silintaphin-1 in biomimetic biomineralization. Biomaterials 30:1648–1656PubMedGoogle Scholar
  153. Wiens M, Wang X, Natalio F, Schröder HC, Schloßmacher U, Wang S, Korzhev M, Geurtsen W, Müller WEG (2010a) Bioinspired fabrication of bio-silica-based bone substitution materials. Adv Eng Mater 12:B438–B450Google Scholar
  154. Wiens M, Wang X, Schloßmacher U, Lieberwirth I, Glasser G, Ushijima H, Schröder HC, Müller WEG (2010b) Osteogenic potential of biosilica on human osteoblast-like (SaOS-2) cells. Calcif Tissue Int 87:513–524PubMedGoogle Scholar
  155. Wiens M, Wang X, Schröder HC, Kolb U, Schloßmacher U, Ushijima H, Müller WEG (2010c) The role of biosilica in the osteoprotegerin/RANKL ratio in human osteoblast-like cells. Biomaterials 31:7716–7725PubMedGoogle Scholar
  156. Woesz A, Weaver JC, Kazanci M, Dauphin Y, Aizenberg J, Morse DE, Fratzl P (2006) Hierarchical assembly of the siliceous skeletal lattice of the hexactinellid sponge Euplectella aspergillum. J Mater Res 21:2068–2078Google Scholar
  157. Wittrant Y, Theoleyre S, Chipoy C, Padrines M, Blanchard F, Heymann D, Redini F (2004) RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis. Biochim Biophys Acta 1704:49–57PubMedGoogle Scholar
  158. Wolf SE, Schlossmacher U, Pietuch A, Mathiasch B, Schröder HC, Müller WEG, Tremel W (2010) Formation of silicones mediated by the sponge enzyme silicatein-α. Dalton Trans 39:9245–9249PubMedGoogle Scholar
  159. Zou S, Ireland D, Brooks RA, Rushton N, Best S (2009) The effects of silicate ions on human osteoblast adhesion, proliferation, and differentiation. J Biomed Mater Res B Appl Biomater 90:123–130PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Heinz C. Schröder
    • 1
    • 2
    Email author
  • Matthias Wiens
    • 3
    • 4
  • Xiaohong Wang
    • 3
    • 5
  • Ute Schloßmacher
    • 3
  • Werner E. G. Müller
    • 1
    • 2
    Email author
  1. 1.ERC Advanced Grant Research Group, Institute for Physiological ChemistryUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
  2. 2.NanotecMARIN GmbHMainzGermany
  3. 3.Institute for Physiological ChemistryUniversity Medical Center of the Johannes Gutenberg University MainzMainzGermany
  4. 4.NanotecMARIN GmbHMainzGermany
  5. 5.National Research Center for GeoanalysisBeijingChina

Personalised recommendations