Skip to main content

Advertisement

SpringerLink
Log in

Association of Calcium and Phosphate Ions with Collagen in the Mineralization of Vertebrate Tissues

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Among the vertebrate species, collagen is the most abundant protein and is associated with mineralization of their skeleton and dentition in all tissues except enamel. In such tissues, bones, calcifying tendon, dentin, and cementum are comprised principally of type I collagen, which has been proposed as a template for apatite mineral formation. Recent considerations of the interaction between type I collagen and calcium and phosphate ions as the major constituents of apatite have suggested that collagen polypeptide stereochemistry underlies binding of these ions at sites within collagen hole and overlap regions and leads to nucleation of crystals. The concept is fundamental to understanding both normal and abnormal mineralization, and it is reviewed in this article. Given this background, avenues for additional research studies in vertebrate mineralization will also be described. The latter include, for instance, how mineralization events subsequent to nucleation, that is, crystal growth and development, occur and whether they, too, are directed by collagen stereochemical parameters; whether mineralization can be expected in all spaces between collagen molecules; whether the side chains of charged amino acid residues actually point toward and into the hole and overlap collagen spaces to provide putative binding sites for calcium and phosphate ions; and what phenomena may be responsible for mineralization beyond hole and overlap zones and into extracellular tissue regions between collagen structural units. These questions will be discussed to provide a broader understanding of collagen contributions to potential mechanisms of vertebrate mineralization.

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

Similar content being viewed by others

References

  1. Robinson RA (1952) An electron-microscope study of the crystalline inorganic component of bone and its relationship to the organic matrix. J Bone Joint Surg 34:389–434

    PubMed  Google Scholar 

  2. Robinson RA, Watson ML (1952) Collagen-crystal relationships in bone as seen in the electron microscope. Anat Rec 114:383–410

    Article  PubMed  CAS  Google Scholar 

  3. Hodge AJ, Petruska JA (1963) Recent studies with the electron microscope on ordered aggregates of the tropocollagen macromolecule. In: Ramachandran GN (ed) Aspects of protein structure. Academic Press, New York, pp 289–300

    Google Scholar 

  4. Glimcher MJ, Krane SM (1968) The organization and structure of bone, and the mechanism of calcification. In: Ramachandran GN, Gould BS (eds) Biology of collagen. Treatise on collagen, vol IIB. Academic Press, New York, pp 68–251

    Google Scholar 

  5. Hodge AJ (1989) Molecular models illustrating the possible distribution of “holes” in simple systematically staggered arrays of type I collagen molecules in native-type fibrils. Connect Tissue Res 21:137–147

    Article  PubMed  CAS  Google Scholar 

  6. Eyre D (1987) Collagen cross-linking amino acids. Methods Enzymol 144:115–139

    Article  PubMed  CAS  Google Scholar 

  7. Yamauchi M, Katz EP, Otsubo K, Teraoka K, Mechanic GL (1989) Cross-linking and stereospecific structure of collagen in mineralized and nonmineralized skeletal tissues. Connect Tissue Res 21:159–169

    Article  PubMed  CAS  Google Scholar 

  8. Weiner S, Traub W (1986) Organization of hydroxyapatite crystals within collagen fibrils. FEBS Lett 206:262–266

    Article  PubMed  CAS  Google Scholar 

  9. McEwen BF, Song MJ, Landis WJ (1992) Quantitative determination of the mineral distribution in different collagen zones of calcifying tendon using high voltage electron microscopic tomography. J Comput Assist Microsc 3:201–210

    Google Scholar 

  10. Landis WJ, Song MJ, Leith A, McEwen L, McEwen B (1993) Mineral and organic matrix interaction in normally calcifying tendon visualized in three dimensions by high voltage electron microscopic tomography and graphic image reconstruction. J Struct Biol 110:39–54

    Article  PubMed  CAS  Google Scholar 

  11. Landis WJ, Hodgens KJ, Song MJ, Arena J, Kiyonaga S, Marko M, Owen C, McEwen BF (1996) Mineralization of collagen occurs on fibril surfaces: evidence from conventional and high voltage electron microscopy and three-dimensional imaging. J Struct Biol 117:24–35

    Article  PubMed  CAS  Google Scholar 

  12. Weiner S, Price P (1986) Disaggregation of bone into crystals. Calcif Tissue Int 39:365–375

    Article  PubMed  CAS  Google Scholar 

  13. Landis WJ, Moradian-Oldak J, Weiner S (1991) Topographic imaging of mineral and collagen in the calcifying turkey tendon. Connect Tissue Res 25:181–196

    Article  PubMed  CAS  Google Scholar 

  14. Silver FH, Landis WJ (2011) Deposition of apatite in collagenous extracellular matrices: identification of possible nucleation sites on type I collagen. Connect Tissue Res 52:242–252

    Article  PubMed  CAS  Google Scholar 

  15. Wang Y, Azaïs T, Robin M, Vallée A, Catania C, Legriel P, Pehau-Arnaudet G, Babonneau F, Giraud-Guille M-M, Nassif N (2012) The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite. Nat Mater 11:724–733

    Article  PubMed  CAS  Google Scholar 

  16. Orgel JPRO, Miller A, Irving TC, Fischetti RF, Hammersley AP, Wess TJ (2001) The in situ supermolecular structure of type I collagen. Structure 9:1061–1069

    Article  PubMed  CAS  Google Scholar 

  17. Orgel JPRO, Irving TC, Miller A, Wess TJ (2006) Microfibrillar structure of type I collagen in situ. Proc Natl Acad Sci USA 103:9001–9005

    Article  PubMed  CAS  Google Scholar 

  18. Meek KM, Chapman JA, Hardcastle RA (1979) The staining pattern of collagen fibrils. J Biol Chem 254:10710–10714

    PubMed  CAS  Google Scholar 

  19. Landis WJ, Silver FH (2002) The structure and function of normally mineralizing avian tendons. Comp Biochem Physiol A Mol Integr Physiol 133:1135–1157

    Article  PubMed  Google Scholar 

  20. Landis WJ (1986) A study of calcification in the leg tendons from the domestic turkey. J Ultrastruct Mol Struct Res 94:217–238

    Article  PubMed  CAS  Google Scholar 

  21. Glimcher MJ (1976) Composition, structure, and organization of bone and mineralized tissues and the mechanism of calcification. In: Greep RO, Astwood EB (eds) Handbook of physiology: endocrinology, vol 3. American Physiological Society, Washington DC, pp 25–116

    Google Scholar 

  22. Glimcher MJ (1989) Mechanism of calcification: role of collagen fibrils and collagen-phosphoprotein complexes in vitro and in vivo. Anat Rec 224:139–153

    Article  PubMed  CAS  Google Scholar 

  23. Strates B, Neuman WF (1958) On the mechanisms of calcification. Proc Soc Exp Biol Med 97:688–691

    Article  PubMed  CAS  Google Scholar 

  24. Fleish H, Neuman WF (1961) Mechanisms of calcification: role of collagen, polyphosphates, and phosphatase. Am J Physiol 200:1296–1300

    PubMed  CAS  Google Scholar 

  25. Sikiric MD, Furedi-Milhofer H (2006) The influence of surface active molecules on the crystallization of biominerals in solution. Adv Colloid Interface Sci 128–130:135–158

    Article  PubMed  Google Scholar 

  26. Fisher LW, Torchia DA, Fohr B, Young MF, Fedarko NS (2001) Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Biochem Biophys Res Commun 280:460–465

    Article  PubMed  CAS  Google Scholar 

  27. Fisher LW, Fedarko NS (2003) Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins. Connect Tissue Res 44:33–40

    PubMed  CAS  Google Scholar 

  28. Chen Y, Bal BS, Gorski JP (1992) Calcium and collagen binding properties of osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 from bone. J Biol Chem 267:24871–24878

    PubMed  CAS  Google Scholar 

  29. Hunter GK, Goldberg HA (1993) Nucleation of hydroxyapatite by bone sialoprotein. Proc Natl Acad Sci USA 90:8562–8565

    Article  PubMed  CAS  Google Scholar 

  30. Hunter GK, Goldberg HA (1994) Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein. Biochem J 302:175–179

    PubMed  CAS  Google Scholar 

  31. Fujisawa R, Nodasaka Y, Kuboki Y (1995) Further characterization of interaction between bone sialoprotein (BSP) and collagen. Calcif Tissue Int 56:140–144

    Article  PubMed  CAS  Google Scholar 

  32. Ganss B, Kim RH, Sodek J (2000) Bone sialoprotein. Crit Rev Oral Biol Med 10:79–98

    Article  Google Scholar 

  33. Tye CE, Hunter GK, Goldberg HA (2005) Identification of the type I collagen-binding domain of bone sialoprotein and characterization of the mechanism of interaction. J Biol Chem 280:13487–13492

    Article  PubMed  CAS  Google Scholar 

  34. George A, Veis A (2008) Phosphorylated proteins and control over apatite nucleation, crystal growth, and inhibition. Chem Rev 108:4670–4693

    Article  PubMed  CAS  Google Scholar 

  35. Hunter GK, Hauschka PV, Poole AR, Rosenberg LC, Goldberg HA (1996) Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochem J 317:59–64

    PubMed  CAS  Google Scholar 

  36. Nanci A, Zalzal S, Gotoh Y, McKee MD (1996) Ultrastructural characterization and immunolocalization of osteopontin in rat calvarial osteoblast primary cultures. Microsc Res Tech 33:214–231

    Article  PubMed  CAS  Google Scholar 

  37. McKee MD, Zalzal S, Nanci A (1996) Extracellular matrix in tooth cementum and mantle dentin: localization of osteopontin and other noncollagenous proteins, plasma proteins, and glycoconjugates by electron microscopy. Anat Rec 245:293–312

    Article  PubMed  CAS  Google Scholar 

  38. Sodek J, Ganss B, McKee MD (2000) Osteopontin. Crit Rev Oral Biol Med 11:279–303

    Article  PubMed  CAS  Google Scholar 

  39. George A, Bannon L, Sabsay B, Dillon JW, Malone J, Veis A, Jenkins NA, Gilbert DJ, Copeland NG (1996) The carboxy-terminal domain of phosphophoryn contains unique extended triplet amino acid repeat sequences forming ordered carboxyl-phosphate interaction ridges that may be essential in the biomineralization process. J Biol Chem 271:32869–32873

    Article  PubMed  CAS  Google Scholar 

  40. Vekilov PG (2004) Dense liquid precursor for the nucleation of ordered solid phases from solution. Crystal Growth Des 4:671–685

    Article  CAS  Google Scholar 

  41. Dey A, Bomans PHH, Muller FA, Will J, Frederik PM, de With G, Sommerdijk NAJM (2010) The role of prenucleation clusters in surface-induced calcium phosphate crystallization. Nat Mater 9:1010–1014

    Article  PubMed  CAS  Google Scholar 

  42. Nudelman F, Pieterse K, George A, Bomans PHH, Friedrich H, Brylka LI, Hilbers PAJ, de With G, Sommerdijk NAJM (2010) The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors. Nat Mater 9:1004–1009

    Article  PubMed  CAS  Google Scholar 

  43. Gower LB (2008) Biomimetic model systems for investigating the amorphous precursor pathway and its role in biomineralization. Chem Rev 108:4551–4627

    Article  PubMed  CAS  Google Scholar 

  44. Zeiger DN, Miles WC, Eidelman N, Lin-Gibson S (2011) Cooperative calcium phosphate nucleation within collagen molecules. Langmuir 27:8263–8268

    Article  PubMed  CAS  Google Scholar 

  45. Toroian D, Lim JE, Price PA (2007) The size exclusion characteristics of type I collagen: implications for the role of noncollagenous bone constituents in mineralization. J Biol Chem 282:22437–22447

    Article  PubMed  CAS  Google Scholar 

  46. Price PA, Toroian D, Lim JE (2009) Mineralization by inhibitor exclusion: the calcification of collagen with fetuin. J Biol Chem 284:17092–17101

    Article  PubMed  CAS  Google Scholar 

  47. Jahnen-Dechent W, Heiss A, Schafer C, Ketteler M (2011) Fetuin-A regulation of calcified matrix metabolism. Circ Res 108:1494–1509

    Article  PubMed  CAS  Google Scholar 

  48. Seto J, Busse B, Gupta HS, Schafer C, Krauss S, Dunlop JW, Masic A, Kerschnitzki M, Zaslansky P, Boesecke P, Catala-Lehnen P, Schinke T, Fratzl P, Jahnen-Dechent W (2012) Accelerated growth plate mineralization and foreshortened proximal limb bones in fetuin-a knockout mice. PLoS One 7:e47338

    Article  PubMed  CAS  Google Scholar 

  49. Traub W, Jodaikin A, Arad T, Veis A, Sabsay B (1992) Dentin phosphophoryn binding to collagen fibrils. Matrix 12:197–201

    Article  PubMed  CAS  Google Scholar 

  50. Kalmar L, Homola D, Varga G, Tompa P (2012) Structural disorder in proteins brings order to crystal growth in biomineralization. Bone 51:528–534

    Article  PubMed  CAS  Google Scholar 

  51. Lees S (1987) Considerations regarding the structure of the mammalian mineralized osteoid from viewpoint of the generalized packing model. Connect Tissue Res 16:281–303

    Article  PubMed  CAS  Google Scholar 

  52. Nylen MJ, Scott DB, Mosely VM (1960) Mineralization of turkey leg tendon. II. Collagen–mineral relations as revealed by electron and X-ray microscopy. In: Sognnaes RF (ed) Calcification in biological systems. American Association for the Advancement of Science, Washington DC, pp 129–142

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Polymer Science, Goodyear Polymer Center, University of Akron, Room 1201C, 170 University Avenue, Akron, OH, 44325-3909, USA

    William J. Landis & Robin Jacquet

Authors
  1. William J. Landis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robin Jacquet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William J. Landis.

Additional information

The authors have stated that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Landis, W.J., Jacquet, R. Association of Calcium and Phosphate Ions with Collagen in the Mineralization of Vertebrate Tissues. Calcif Tissue Int 93, 329–337 (2013). https://doi.org/10.1007/s00223-013-9725-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-013-9725-7

Keywords

Search

Navigation