Abstract
Fluoride had been shown to inhibit collagen-induced in vitro mineralization without affecting demineralization at its lower concentrations (> 1X10-5 and < 1X10-4 M) and stimulate mineralization in addition to inhibiting demineralization at its concentration > 1X10-4 M. The present studies were designed to investigate the mechanism by which fluoride acts to produce these concentration-dependent effects. The inhibition of mineralization occurring at the lower concentrations of fluoride was found to be due to the inactivation of the specific calcium binding sites of collagen involved in initiating the process of mineralization. Stimulation of mineralization obtained at the higher concentrations of fluoride was found to be due to the activation of the specific phosphate-binding sites of the collagen and the formation of a relatively less soluble and highly stable fluorapatite instead of hydroxyapatite. At its higher concentrations, fluoride was also found to inhibit demineralization by binding to the mineral phase associated with collagen. A model has been presented to explain the mechanisms whereby fluoride may act to produce the above observed effects.
Similar content being viewed by others
References
Abou Neel EA, Aljabo A, Strange A, Ibrahim S, Coathup M, Young AM, Bozec L, Mudera V (2016) Demineralization-remineralization dynamics in teeth and bone. Int J Nanomedicine 11:4743–4763. https://doi.org/10.2147/IJN.S107624
Dorozhkin SV, Epple M (2002) Biological and medical significance of calcium phosphates. Angew Chem Int Ed Engl 41(17):3130–3146. https://doi.org/10.1002/1521-3773(20020902)41:17<3130::AID-ANIE3130>3.0.CO;2-1
KokuboT (2008) Bioceramics and Their Clinical Applications (1st ed.). Woodhead Publishing Limited United Kingdom, Cambridge. https://www.elsevier.com/books/bioceramics-and-their-clinical-applications/kokubo/978-1-84569-204-9
Margolis HC, Kwak SY, Yamazaki H (2014) Role of mineralization inhibitors in the regulation of hard tissue biomineralization: relevance to initial enamel formation and maturation. Front Physiol 5:339. https://doi.org/10.3389/fphys.2014.00339
Gelse K, Pöschl E, Aigner T (2003) Collagens - structure, function, and biosynthesis. Adv Drug Deliv Rev 55(12):1531–1546
Glimcher MJ (1959) Molecular biology of mineralized tissues with particular reference to bone. Rev Mod Phys 31(2):359–393
Singh SP, Singh R, Jethi RK (1982) Kinetics of in vitro aorta mineralization. Indian J Exp Biol 20(9):691–695
Talwar HS, Jethi RK (1978) Role of collagen in ion uptake & exchange reactions. Indian J Exp Biol 16(2):187–190
Jethi RK, Inlow CW, Wadkins CL (1970) Studies of the mechanism of biological calcification. Calcif Tissue Res 6(1):81–92
Jethi RK, Wadkins CL (1971) Studies of the mechanism of biological calcification. Calcif Tissue Res 7(1):277–289
Hunter GK, Hauschka PV, Poole AR, Rosenberg LC, Goldberg HA (1996) Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochem J 317(Pt 1):59–64. https://doi.org/10.1042/bj3170059
Nudelman F, Pieterse K, George A, Bomans PH, Friedrich H, Brylka LJ et al (2010) The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors. Nat Mater 9(12):1004–1009. https://doi.org/10.1038/nmat2875
Alliston T (2014) Biological Regulation of Bone Quality. Curr Osteoporos Rep 12(3):366–375. https://doi.org/10.1007/s11914-014-0213-4
Wang Y, Azaïs T, Robin M, Vallée A, Catania C, Legriel P et al (2012) The predominant role of collagenin the nucleation, growth, structureand orientationofbone apatite. Nat Mater 11(8):724–733. https://doi.org/10.1038/nmat3362
Jethi RK, Chander L, Singh J (1977) Kinetic evidence for a step-wise process in collagen-induced in vitro calcification. Indian J Exp Biol 15(1):35–39
Blumenthal NC (1989) Mechanisms of inhibition of calcification. Clin Orthop Relat Res NA(247):279–289
Gupta LC, Singla SK, Tandon C, Jethi RK (2004) Mg2+: a potent inhibitor of collagen-induced in vitro mineralization. Magnes Res 17(2):67–71
Tandon CD, Forouzandeh M, Aggarwal S, Jethi RK (1997) Inhibitors of in vitro mineralization from flexor tendons of rabbits and their role in biological mineralization. Mol Cell Biochem 171(1–2):29–35
Aggarwal S, Tandon CD, Forouzandeh M, Singla SK, Kiran R, Jethi RK (2000) Role of biomolecules from human renal stone matrix on COM crystal growth. Mol Cell Biochem 210(1–2):109–119
Moghadam MF, Tandon C, Aggarwal S, Singla SK, Singh SK, Sharma SK, Varshney GC, Jethi RK (2003) Concentration of a potent calcium oxalate monohydrate crystal growth inhibitor in the urine of normal persons and kidney stone patients by ELISA-based assay system employing monoclonal antibodies. J Cell Biochem 90(6):1261–1275
McGaughey C (1983) Binding of polyphosphates and phosphonates to hydroxyapatite, subsequent hydrolysis, phosphate exchange and effects on demineralization, mineralization and microcrystal aggregation. Caries Res 17(3):229–241
Kakkar M, Kapoor V, Singla SK, Jethi RK (2020) Fluoride and Biological Calcification I: Effect of Fluoride on Collagen-Induced In Vitro Mineralization and Demineralization Reactions. Biol Trace Elem Res. https://doi.org/10.1007/s12011-020-02340-3
Baginski ES, Marie SS, Clark WL, Zak B (1973) Direct microdetermination of serum calcium. Clin Chim Acta 46(1):46–54
Amador E, Urban J (1972) Simplified serum phosphorus analyses by continuous-flow ultraviolet spectrophotometry. Clin Chem 18(7):601–604
Kirk KL (1991) Biochemistry of inorganic fluoride. In: Biochemistry of the elemental halogens and inorganic halides. Springer US, Boston, pp 19–68
Everett ET (2011) Fluoride’s effects on the formation of teeth and bones, and the Influence of Genetics. J Dent Res 90(5):552–560
Vieira A, Hancock R, Dumitriu M, Schwartz M, Limeback H, Grynpas M (2005) How does fluoride affect dentin microhardness and mineralization? J Dent Res 84(10):951–957
Aoba T (1997) The effect of fluoride on apatite structure and growth. Crit Rev Oral Biol Med 8(2):136–153
Kanduti D, Sterbenk P, Artnik B (2016) Fluoride: a review of use and effects on health. Mater Sociomed 28(2):133–137. https://doi.org/10.5455/msm.2016.28.133-137
Clark MB, Slayton RL (2014) Fluoride use in caries prevention in the primary care setting. Pediatrics 134(3):626–633. https://doi.org/10.1542/peds.2014-1699
Agalakova NI, Gusev GP (2012) Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. ISRN Cell Biol 2012:1–16
Dhar V, Bhatnagar M (2009) Physiology and toxicity of fluoride. Indian J Dent Res 20(3):350–355. https://doi.org/10.4103/0970-9290.57379
Perumal E, Paul V, Govindarajan V, Panneerselvam L (2013) A brief review on experimental fluorosis. Toxicol Lett 223(2):236–251. https://doi.org/10.1016/j.toxlet.2013.09.005
Qin X, Wang S, Yu M, Zhang L, Li X, Zuo Z et al (2009) Child skeletal fluorosis from indoor burning of coal in southwestern China. J Environ Public Health 2009:969764. https://doi.org/10.1155/2009/969764
Krishnamachari KA (1986) Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Prog Food Nutr Sci 10(3–4):279–314
Tomoaia G, Pasca RD (2015) On the Collagen Mineralization. A Review. Clujul Med 88(1):15–22. https://doi.org/10.15386/cjmed-359
Heaney RP, Recker RR, Watson P, Lappe JM (2010) Phosphate and carbonate salts of calcium support robust bone building in osteoporosis. Am J Clin Nutr 92(1):101–105. https://doi.org/10.3945/ajcn.2009.29085
Acknowledgments
Indebted to Mr. K. K. Maheshwari for initiating the work on the project and standardizing the various techniques. Grateful to Department of Biochemistry (PU, Chandigarh and HIMS, Dehradun) for providing required funds and facilities.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that there is no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kakkar, M., Kapoor, V., Singla, S.K. et al. Fluoride and Biological Mineralization II: Mechanism of Action of Fluoride to Influence the Collagen-Induced In Vitro Mineralization and Demineralization Reactions. Biol Trace Elem Res 199, 4145–4153 (2021). https://doi.org/10.1007/s12011-020-02544-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-020-02544-7