Abstract
A variety of in vitro study methods have been used to elucidate the roles of matrix molecules in biomineralization processes. Among these, gel diffusion-precipitation studies have proved to be an effective tool. This methodology is uniquely capable of characterizing the effects of matrix molecules on mineralization while only using very small quantities of material. Furthermore, gel methods have been extended for use as a mineralization assay system to characterize modified matrix molecules and synthetic analogues. Here we discuss the advantages and limitations of gelatin, agar, agarose, and other systems for studying the mechanisms of biomineralization.
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References
AL Boskey M Maresca W Ullrich SB Doty WT Butler CW Prince (1993) ArticleTitleOsteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel Bone Miner 22 147–159 Occurrence Handle1:CAS:528:DyaK2cXnsVagtQ%3D%3D Occurrence Handle8251766
AL Boskey (1995) ArticleTitleOsteopontin and related phosphorylated sialoproteins: effects on mineralization Ann NY Acad Sci 760 249–256 Occurrence Handle1:CAS:528:DyaK2MXovVSitrY%3D Occurrence Handle7785899
GK Hunter A Goldberg (1993) ArticleTitleNucleation of hydroxapatite by bone sialoprotein Proc Natl Acad Sci USA 90 8562–8565
GK Hunter HA Goldberg (1995) ArticleTitleThe inhibitory activity of osteopontin on hydroxyapatite formation in vitro Ann NY Acad Sci 760 305–308 Occurrence Handle7785906
JD Termine K Kleinman SW Whitson KM Conn ML McGarvey GR Martin (1981) ArticleTitleOsteonectin, a bone-specific protein linking mineral to collagen Cell 26 99–105 Occurrence Handle10.1016/0092-8674(81)90037-4 Occurrence Handle1:CAS:528:DyaL38Xhs1amtQ%3D%3D Occurrence Handle7034958
GK Hunter PV Hauschka AR Poole LC Rosenberg HA Goldberg (1996) ArticleTitleNucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins Biochem J 317 59–64 Occurrence Handle1:CAS:528:DyaK28Xktl2mtb8%3D Occurrence Handle8694787
GK Hunter HA Curtis MD Grynpas JP Simmer AG Fincham (1999) ArticleTitleEffects of recombinant amelogenin on hydroxyapatite formation in vitro Calcif Tissue Int 65 226–231 Occurrence Handle10.1007/s002239900688 Occurrence Handle1:CAS:528:DyaK1MXlt1SjsbY%3D Occurrence Handle10441656
M Iijima Y Moriwaki HB Wen AG Fincham J Moradian-Oldak (2002) ArticleTitleElongated growth of octacalcium phosphate crystals in recombinant amelogenin gels under controlled ionic flow J Dent Res 81 69–73 Occurrence Handle1:CAS:528:DC%2BD38XnvFemtA%3D%3D Occurrence Handle11820371
CE Tye KR Rattra KJ Warner JA Gordon J Sodek GK Hunter HA Goldberg (2003) ArticleTitleDelineation of the hydroxyapatite-nucleating domains of bone sialoprotein J Biol Chem 278 7949–7955
JL Arias DJ Fink SQ Xiao AH Heuer AI Caplan (1993) ArticleTitleBiomineralization and eggshells: cell-mediated acellular compartments of mineralized extracellular matrix Int Rev Cytol 145 217–250
BA Gotliv L Addadi S Weiner (2003) ArticleTitleMollusk shell acidic proteins: in search of individual functions Chembiochem 4 522–529 Occurrence Handle10.1002/cbic.200200548 Occurrence Handle1:CAS:528:DC%2BD3sXkslCiuro%3D Occurrence Handle12794863
AL Boskey (1996) ArticleTitleMatrix proteins and mineralization Connect Tissue Res 35 357–363 Occurrence Handle1:CAS:528:DyaK2sXhvFamtbw%3D Occurrence Handle9084675
HK Henisch (1988) Crystals in gels and liesegang rings Cambridge University Press Cambridge
NC Blumenthal AS Posner LD Silverman LC Rosenberg (1979) ArticleTitleEffect of proteoglycans on in vitro hydroxyapatite formation Calcif Tissue Int 27 75–82 Occurrence Handle1:CAS:528:DyaE1MXitVWnt78%3D Occurrence Handle111791
Z Amjad P Koutsoukos MB Tomson GH Nancollas (1978) ArticleTitleThe growth of hydroxyapatite from solution. A new constant composition method J Dent Res 57 909 Occurrence Handle1:CAS:528:DyaE1MXltFSmsQ%3D%3D Occurrence Handle281366
AL Boskey (1989) ArticleTitleHydroxyapatite formation in a dynamic collagen gel system: effects of type I collagen, lipids, and proteoglycans J Phys Chem 93 1628–1633 Occurrence Handle1:CAS:528:DyaL1MXptFKjtQ%3D%3D
GS Mandel PB Halverson NS Mandel (1988) ArticleTitleCalcium pyrophosphate crystal deposition: the effect of monosodium urate and apatite crystals in a kinetic study using a gelatin matrix model Scanning Microsc 2 1189–1198 Occurrence Handle1:CAS:528:DyaL1cXktlKju7w%3D Occurrence Handle2840735
NS Mandel GS Mandel DJ Carroll PB Halverson (1984) ArticleTitleCalcium pyrophosphate crystal deposition. An in vitro study using a gelatin matrix model Arthritis Rheum 27 789–796 Occurrence Handle1:CAS:528:DyaL2cXlt1ygurw%3D Occurrence Handle6331461
Z Pucar B Pokric A Graovac (1974) ArticleTitlePrecipitation in gels under conditions of double diffusion: critical concentrations of the precipitating components Anal Chem 46 403–407 Occurrence Handle1:CAS:528:DyaE2cXhtVSmurs%3D
AL Boskey M Maresca S Doty B Sabsay A Veis (1990) ArticleTitleConcentration-dependent effects of dentin phosphophoryn in the regulation of in vitro hydroxyapatite formation and growth Bone Miner 11 55–65 Occurrence Handle10.1016/0169-6009(90)90015-8 Occurrence Handle1:CAS:528:DyaK3MXpvVygtA%3D%3D Occurrence Handle2176557
AL Boskey L Spevak SB Doty L Rosenberg (1997) ArticleTitleEffects of bone CS-proteoglycans, DS-decorin, and DS-biglycan on hydroxyapatite formation in gelatin gel Calcif Tissue Int 61 298–305 Occurrence Handle10.1007/s002239900339 Occurrence Handle1:CAS:528:DyaK2sXmsFCltbw%3D Occurrence Handle9312200
AL Boskey L Spevak M Tan SB Doty WT Butler (2000) ArticleTitleDentin sialoprotein (DSP) has limited effects on in vitro apatite formation and growth Calcif Tissue Int 67 472–478 Occurrence Handle10.1007/s002230001169 Occurrence Handle1:CAS:528:DC%2BD3MXhvVOruro%3D Occurrence Handle11289697
PH Tartaix M Doulaverakis A George et al. (2004) ArticleTitleIn vitro effects of dentin matrix protein-1 on hydroxyapatite formation provide insights into in vivo functions J Biol Chem 279 18115–18120
AL Boskey BD Boyan Z Schwartz (1997) ArticleTitleMatrix vesicles promote mineralization in a gelatin gel system Calcif Tissue Int 60 309–315 Occurrence Handle10.1007/s002239900234 Occurrence Handle1:CAS:528:DyaK2sXhsFKgtLY%3D Occurrence Handle9069171
EM Greenfield DC Wilson MA Crenshaw (1984) ArticleTitleIonotropic nucleation of calcium carbonate by molluscan matrix Am Zool 24 925–932 Occurrence Handle1:CAS:528:DyaL2MXptleisA%3D%3D
L Addadi S Weiner M Geva (2001) ArticleTitleOn how proteins interact with crystals and their effect on crystal formation Z Kardiol 90 IssueIDsuppl 3 392–398 Occurrence Handle10.1007/s003920170049
L Addadi S Weiner (1985) ArticleTitleInteractions between acidic proteins and crystals: stereochemical requirements in biomineralization Proc Natl Acad Sci USA 88 4110–4114
GK Hunter CL Kyle HA Goldberg (1994) ArticleTitleModulation of crystal formation by bone phosphoproteins: structural specificity of the osteopontin-mediated inhibition of hydroxyapatite formation Biochem J 300 723–728 Occurrence Handle1:CAS:528:DyaK2cXkt12mt78%3D Occurrence Handle8010953
HA Goldberg KJ Warner MJ Stillman GK Hunter (1996) ArticleTitleDetermination of the hydroxyapatite-nucleating region of bone sialoprotein Connect Tissue Res 35 385–392 Occurrence Handle1:CAS:528:DyaK2sXhvFals70%3D Occurrence Handle9084679
GK Hunter HA Goldberg (1994) ArticleTitleModulation of crystal formation by bone phosphoproteins: role for glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein Biochem J 302 175–179 Occurrence Handle1:CAS:528:DyaK2cXltlSktrw%3D Occurrence Handle7915111
NL Harris KR Rattray CE Tye TM Underhill MJ Somerman JA D’Errico AI Chambers GK Hunter FA Goldberg (2000) ArticleTitleFunctional analysis of bone sialoprotein: identification of the hydroxyapatite-nucleating and cell-binding domains by recombhiant peptide expression and site-directed mutagenesis Bone 27 795–802 Occurrence Handle10.1016/S8756-3282(00)00392-6 Occurrence Handle1:CAS:528:DC%2BD3cXosFCisbs%3D Occurrence Handle11113390
Y Wada R Fujisawa Y Nodasaka Y Kuboki (1996) ArticleTitleElectrophoretic gels of dentin matrix proteins as diffusion media for in vitro mineralization J Dent Res 75 1381–1387 Occurrence Handle1:CAS:528:DyaK28XmsVOqtbo%3D Occurrence Handle8831633
R Fujisawa Y Kuboki S Sasaki (1987) ArticleTitleEffects of dentin phosphophoryn on precipitation of calcium phosphate in gel in vitro Calcif Tissue Int 41 44–47
AL Boskey M Maresca J Appel (1989) ArticleTitleThe effects of noncollageneous matrix proteins on hydroxyapatite formation and proliferation in a collagen gel system Connect Tissue Res 21 171–178 Occurrence Handle1:STN:280:By%2BC3cjktlY%3D Occurrence Handle2605941
R Fujisawa Y Wada Y Nodasaka Y Kuboki (1996) ArticleTitleAcidic amino acid-rich sequences as binding sites of osteonectin to hydroxyapatite crystals Biochim Biophys Acta 1292 53–60 Occurrence Handle10.1016/0167-4838(95)00190-5 Occurrence Handle1:CAS:528:DyaK28Xhsl2ksA%3D%3D Occurrence Handle8547349
D Couchourel C Escoffier R Rohanizadeh S Bohic G Daculsi Y Fortun M Padrines (1999) ArticleTitleEffects of fibronectin on hydroxyapatite formation J Inorg Biochem 73 129–136 Occurrence Handle10.1016/S0162-0134(99)00006-9 Occurrence Handle1:CAS:528:DyaK1MXjtFChtr0%3D Occurrence Handle10331242
T Taira M Iijima Y Moriwaki Y Kuboki (1995) ArticleTitleA new method for in vitro calcification using acrylamide gel and bovine serum Connect Tissue Res 33 185–192 Occurrence Handle1:STN:280:BymD3s3htlQ%3D Occurrence Handle7554952
N Bouropoulos J Moradian-Oldak (2004) ArticleTitleInduction of apatite by the cooperative effect of amelogenin and the 32-kDa enamelin J Dent Res 83 278–282 Occurrence Handle1:CAS:528:DC%2BD2cXjs1ClurY%3D Occurrence Handle15044499
M Iijima Y Moriwaki T Takagi J Moradian-Oldak (2001) ArticleTitleEffects of bovine amelogenins on the crystal morphology of octacalcium phosphate in a model system of tooth enamel formation J Cryst Growth 222 615–626 Occurrence Handle10.1016/S0022-0248(00)00984-2 Occurrence Handle1:CAS:528:DC%2BD3MXksFKjuw%3D%3D
HB Wen J Moradian-Oldak AG Fincham (2000) ArticleTitleDose-dependent modulation of octacalcium phosphate crystal habit by ameloginins J Dent Res 79 1902–1906 Occurrence Handle1:CAS:528:DC%2BD3MXktFKmtQ%3D%3D Occurrence Handle11145363
G He T Dahl A Veis A Geogre (2003) ArticleTitleNucleation of apatite crystals in vitro by self-assembled dentin matrix protein-1 Nat Mater 2 552–558 Occurrence Handle10.1038/nmat945 Occurrence Handle1:CAS:528:DC%2BD3sXlvFaku78%3D Occurrence Handle12872163
D Srzic B Pokric Z Pucar (1976) ArticleTitlePrecipitation in gels under conditions of double diffusion: critical concentrations and solubility products of salts Z Physi Chem 103 157–164 Occurrence Handle1:CAS:528:DyaE2sXht1OrtLg%3D
B Pokric Z Pucar (1979) ArticleTitlePrecipitation of calcium phosphate under conditions of double diffusion in collagen and gels of gelatin and agar Calcif Tissue Int 27 171–176 Occurrence Handle1:CAS:528:DyaE1MXkvVynsLk%3D Occurrence Handle110419
P Somasundaran YHC Wang (1984) Surface chemical characteristics and adsorption properties of apatite DN Misra (Eds) Adsorption on and surface chemistry of hydroxyapatite Plenum Press New York 129
DT Hughes Wassell RC Hall G Embery (1995) ArticleTitleAdsorption of bovine serum albumin onto hydroxyapatite Biomaterials 16 697–702 Occurrence Handle10.1016/0142-9612(95)99697-K Occurrence Handle7578773
GK Hunter SC Nyburg KPH Pritzker (1986) ArticleTitleHydroxyapatite formation in collagen, gelatin, and agarose gels Coll Rel Res 61 229–238
S Eiden-Abmann M Viertelhaus A Heiß KA Hoetzer J Felsche (2002) ArticleTitleThe influence of amino acids on the biomineralization of hydroxyapatite in gelatin J Inorg Biochem 91 481–486 Occurrence Handle10.1016/S0162-0134(02)00481-6 Occurrence Handle12175941
R Fujisawa Y Nodasake Y Kuboki (1995) ArticleTitleFurther characterization of interaction between bone sialoprotein (BSP) and collagen Calcif Tissue Int 56 140–144 Occurrence Handle1:CAS:528:DyaK2MXkvVylu7c%3D Occurrence Handle7736323
T Saito M Yamauchi MA Crenshaw (1998) ArticleTitleApatite induction by insoluble dentin collagen J Bone Miner Res 13 265–270 Occurrence Handle1:CAS:528:DyaK1cXhtlSltr8%3D Occurrence Handle9495520
T Saito AL Arsenault M Yamauchi Y Kuboki MA Crenshaw (1997) ArticleTitleMineral induction by immobilized phosphoproteins Bone 21 305–311 Occurrence Handle10.1016/S8756-3282(97)00149-X Occurrence Handle1:CAS:528:DyaK2sXnt1Klt74%3D Occurrence Handle9315333
A Linde A Lussi MA Crenshaw (1989) ArticleTitleMineral induction by immobilized polyanionic proteins Calcif Tissue Int 44 286–295 Occurrence Handle1:CAS:528:DyaL1MXktVakur8%3D Occurrence Handle2501010
A Lussi MA Crenshaw A Linde (1988) ArticleTitleInduction and inhibition of hydroxyapatite formation by rat dentine phosphoprotein in vitro Arch oral Biol 33 685–691 Occurrence Handle10.1016/0003-9969(88)90124-0 Occurrence Handle1:CAS:528:DyaL1cXmt1Onuro%3D Occurrence Handle3245795
Acknowledgments
The authors wish to acknowledge the help of Melin Tan, Hospital for Special Surgery, and Aryeh Keehn, Yeshiva University, for their contributions exploring single diffusion gelatin systems. Dr Boskey’s work discussed in this paper was supported by NIH grant DE04141.
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Silverman, L., Boskey, A.L. Diffusion Systems for Evaluation of Biomineralization. Calcif Tissue Int 75, 494–501 (2004). https://doi.org/10.1007/s00223-004-0019-y
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DOI: https://doi.org/10.1007/s00223-004-0019-y