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Fibroblast Growth Factor 2 High Molecular Weight Isoforms in Dentoalveolar Mineralization

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Abstract

Transgenic mice overexpressing human high molecular weight fibroblast growth factor 2 (HMWFGF2) isoforms in osteoblast and odontoblast lineages (HMWTg) exhibit decreased dentin and alveolar bone mineralization, enlarged pulp chamber, and increased fibroblast growth factor 23 (FGF23). We examined if the alveolar bone and dentin mineralization defects in HMWTg mice resulted from increased FGF23 expression and whether an FGF23 neutralizing antibody could rescue the hypomineralization phenotype. HMWTg and VectorTg control mice were given subcutaneous injections of FGF23 neutralizing antibody twice/week starting at postnatal day 21 for 6 weeks. Since Calcitriol (1,25D) have direct effects in promoting bone mineralization, we also determined if 1,25D protects against the defective dentin and alveolar bone mineralization. Therefore, HMWTg mice were given subcutaneous injections of 1,25D daily or concomitantly with FGF23 neutralizing antibody for 6 weeks. Our results showed that HMWTg mice displayed thickened predentin, alveolar bone hypomineralization, and enlarged pulp chambers. FGF23 neutralizing antibody and 1,25D monotherapy partially rescued the dentin mineralization defects and the enlarged pulp chamber phenotype in HMWTg mice. 1,25D alone was not sufficient to rescue the alveolar bone hypomineralization. Interestingly, HMWTg mice treated with both FGF23 neutralizing antibody and 1.25D further rescued the enlarged pulp chamber size, and dentin and alveolar bone mineralization defects. We conclude that the dentin and alveolar bone mineralization defects in HMWTg mice might result from increased FGF23 expression. Our results show a novel role of HMWFGF2 on dentoalveolar mineralization.

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Acknowledgements

We thank Amgen Inc., Thousand Oaks, CA for supplying the FGF23 neutralizing antibody. NIH Grant DK098566 and Grant R01 AR072985-05 to MMH supported this project. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. University of Connecticut School of Dental Medicine, Farmington, CT, USA

    Grethel Millington

  2. Department of Craniofacial Sciences, University of Connecticut School of Dental Medicine, Farmington, CT, USA

    Anushree Vijaykumar & Mina Mina

  3. Department of Medicine, University of Connecticut School of Medicine, UConn Health, Farmington, CT, 06030-052, USA

    Liping Xiao & Marja M. Hurley

  4. NYU Langone Health, Postdoctoral Pediatric Dentistry Program, Brooklyn, NY, 11220, USA

    Johnny Joseph

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  1. Grethel Millington
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Contributions

GM contributed to study design, data acquisition, analysis, and interpretation; drafted and critically revised the manuscript. JJ contributed to data acquisition and analysis; and critically revised the manuscript. LX contributed to data acquisition, analysis, and interpretation; and critically revised the manuscript. AV contributed to data acquisition and critically revised the manuscript. MM contributed to study design, data analysis, and interpretation; and critically revised the manuscript. MH contributed to study conception and design, data analysis, and interpretation; and critically revised the manuscript. All authors gave their final approval and agree to be accountable for all aspects of the work.

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Correspondence to Grethel Millington or Marja M. Hurley.

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The authors have no financial relationship with any organization and therefore have nothing to disclose. The authors have full control of all primary data and agree to allow the journal to review the data if requested.

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There were no human studies conducted in this manuscript and approval for the animal studies were obtained from The UConn Health Institute of Animal Care and Use Committee.

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Millington, G., Joseph, J., Xiao, L. et al. Fibroblast Growth Factor 2 High Molecular Weight Isoforms in Dentoalveolar Mineralization. Calcif Tissue Int 110, 93–103 (2022). https://doi.org/10.1007/s00223-021-00888-3

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  • DOI: https://doi.org/10.1007/s00223-021-00888-3

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