Bisphosphonate modulates cementoblast behavior in vitro

Yong-hee P Chun, Brian L. Foster, Patricia A. Lukasavage, Janice E. Berry, Ming Zhao, Howard C. Tenenbaum, Martha J. Somerman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Cementum formation is deemed to be instrumental for the successful regeneration of periodontal tissues, and thus events and modifiers of cementum formation and mineralization need to be determined. This study aimed to determine whether the bisphosphonate 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) altered the behavior of immortalized cementoblasts (osteocalcin-cementoblasts [OCCM]). Methods: OCCM from transgenic mice were exposed to HEBP at concentrations ranging from 0.01 to 10.0 μM. The assays performed included the count of cell number for proliferation, Northern blot analysis for gene expression (up to 10 days for core binding factor alpha-1 [Cbfa1], bone sialoprotein [BSP], osteocalcin [OCN], and osteopontin [OPN], markers for cementoblast/osteoblast maturation/mineralization), von Kossa stain and alizarin red S stain for mineralization, and enzyme assay (p-nitrophenol phosphate cleavage) for alkaline phosphatase (ALP) activity. Results: Mineral nodule formation was inhibited at the higher doses of HEBP (1.0 and 10.0 μM) only. At early stages (1, 3, and 6 days), gene expression assays revealed only subtle changes in treated cells versus untreated cells, but by day 10, groups treated with lower doses (0.01 and 0.1 μM) were markedly different at the gene expression level. OCN was significantly downregulated (70%) at the lowest dose, with less pronounced effects at higher doses. In concurrence, the master switch gene for osteoblasts, Cbfa1, was also down-regulated at the lower doses. Inversely, OPN mRNA was enhanced at the lower doses. ALP activity was not altered by HEBP. Conclusion: Bisphosphonate alters cementoblast function in vitro through the regulation of gene expression and mineral formation.

Original languageEnglish (US)
Pages (from-to)1890-1900
Number of pages11
JournalJournal of Periodontology
Volume76
Issue number11
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Dental Cementum
Diphosphonates
Osteocalcin
Osteopontin
Osteoblasts
Gene Expression
Minerals
Alkaline Phosphatase
Coloring Agents
Switch Genes
Etidronic Acid
Enzyme Assays
Gene Expression Regulation
In Vitro Techniques
Northern Blotting
Transgenic Mice
Regeneration
Down-Regulation
Cell Count
Cell Proliferation

Keywords

  • Bisphosphonate
  • Cementoblasts
  • Drug effects
  • Gene expression
  • Mineralization

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Chun, Y. P., Foster, B. L., Lukasavage, P. A., Berry, J. E., Zhao, M., Tenenbaum, H. C., & Somerman, M. J. (2005). Bisphosphonate modulates cementoblast behavior in vitro. Journal of Periodontology, 76(11), 1890-1900. https://doi.org/10.1902/jop.2005.76.11.1890

Bisphosphonate modulates cementoblast behavior in vitro. / Chun, Yong-hee P; Foster, Brian L.; Lukasavage, Patricia A.; Berry, Janice E.; Zhao, Ming; Tenenbaum, Howard C.; Somerman, Martha J.

In: Journal of Periodontology, Vol. 76, No. 11, 11.2005, p. 1890-1900.

Research output: Contribution to journalArticle

Chun, YP, Foster, BL, Lukasavage, PA, Berry, JE, Zhao, M, Tenenbaum, HC & Somerman, MJ 2005, 'Bisphosphonate modulates cementoblast behavior in vitro', Journal of Periodontology, vol. 76, no. 11, pp. 1890-1900. https://doi.org/10.1902/jop.2005.76.11.1890
Chun YP, Foster BL, Lukasavage PA, Berry JE, Zhao M, Tenenbaum HC et al. Bisphosphonate modulates cementoblast behavior in vitro. Journal of Periodontology. 2005 Nov;76(11):1890-1900. https://doi.org/10.1902/jop.2005.76.11.1890
Chun, Yong-hee P ; Foster, Brian L. ; Lukasavage, Patricia A. ; Berry, Janice E. ; Zhao, Ming ; Tenenbaum, Howard C. ; Somerman, Martha J. / Bisphosphonate modulates cementoblast behavior in vitro. In: Journal of Periodontology. 2005 ; Vol. 76, No. 11. pp. 1890-1900.
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abstract = "Background: Cementum formation is deemed to be instrumental for the successful regeneration of periodontal tissues, and thus events and modifiers of cementum formation and mineralization need to be determined. This study aimed to determine whether the bisphosphonate 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) altered the behavior of immortalized cementoblasts (osteocalcin-cementoblasts [OCCM]). Methods: OCCM from transgenic mice were exposed to HEBP at concentrations ranging from 0.01 to 10.0 μM. The assays performed included the count of cell number for proliferation, Northern blot analysis for gene expression (up to 10 days for core binding factor alpha-1 [Cbfa1], bone sialoprotein [BSP], osteocalcin [OCN], and osteopontin [OPN], markers for cementoblast/osteoblast maturation/mineralization), von Kossa stain and alizarin red S stain for mineralization, and enzyme assay (p-nitrophenol phosphate cleavage) for alkaline phosphatase (ALP) activity. Results: Mineral nodule formation was inhibited at the higher doses of HEBP (1.0 and 10.0 μM) only. At early stages (1, 3, and 6 days), gene expression assays revealed only subtle changes in treated cells versus untreated cells, but by day 10, groups treated with lower doses (0.01 and 0.1 μM) were markedly different at the gene expression level. OCN was significantly downregulated (70{\%}) at the lowest dose, with less pronounced effects at higher doses. In concurrence, the master switch gene for osteoblasts, Cbfa1, was also down-regulated at the lower doses. Inversely, OPN mRNA was enhanced at the lower doses. ALP activity was not altered by HEBP. Conclusion: Bisphosphonate alters cementoblast function in vitro through the regulation of gene expression and mineral formation.",
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