Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects

S. Abboud Werner, J. Gluhak-Heinrich, K. Woodruff, Y. Wittrant, L. Cardenas, M. Roudier, M. MacDougall

Research output: Contribution to journalArticle

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Abstract

Objective: The aim of this study was to characterize the tooth phenotype of CSF-1-deficient op/op mice and determine whether expression of csCSF-1 in these mice has a role in primary tooth matrix formation. Design: Ameloblasts and odontoblasts, isolated from wt/wt frozen sections using laser capture microdissection, were analysed for csCSF-1, sCSF-1 and CSF-1R mRNA by RT-PCR. Mandibles, excised from 8 days op/op and wt/wt littermates, were examined for tooth morphology as well as amelogenin and DMP1 expression using in situ hybridisation. op/opCS transgenic mice, expressing csCSF-1 in teeth and bone using the osteocalcin promoter, were generated. Skeletal X-rays and histomorphometry were performed; teeth were analysed for morphology and matrix proteins. Results: Normal dental cells in vivo express both CSF-1 isoforms and CSF-1R. Compared to wt/wt, op/op teeth prior to eruption showed altered dental cell morphology and dramatic reduction in DMP1 transcripts. op/opCS mice showed marked resolution of osteopetrosis, tooth eruption and teeth that resembled amelogenesis imperfecta-like phenotype. At 3 weeks, op/op teeth showed severe enamel and dentin defects and barely detectable amelogenin and DMP1. In op/opCS mice, DMP1 in odontoblasts increased to near normal and dentin morphology was restored; amelogenin also increased. Enamel integrity improved in op/opCS, although it was thinner than wt enamel. Conclusions: Results demonstrate that ameloblasts and odontoblasts are a source and potential target of CSF-1 isoforms in vivo. Expression of csCSF-1 within the tooth microenvironment is essential for normal tooth morphogenesis and may provide a mechanism for coordinating the process of tooth eruption with endogenous matrix formation.

Original languageEnglish (US)
Pages (from-to)432-443
Number of pages12
JournalArchives of Oral Biology
Volume52
Issue number5
DOIs
StatePublished - May 2007

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Tooth
Macrophage Colony-Stimulating Factor
Amelogenin
Odontoblasts
Dental Enamel
Ameloblasts
Tooth Eruption
Dentin
Protein Isoforms
Amelogenesis Imperfecta
Osteopetrosis
Laser Capture Microdissection
Phenotype
Deciduous Tooth
Osteocalcin
Frozen Sections
Mandible
Morphogenesis
Transgenic Mice
In Situ Hybridization

Keywords

  • Macrophage colony-stimulating factor (CSF-1)
  • Osteocalcin promoter
  • Osteopetrosis
  • Teeth
  • Transgenic mice

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Werner, S. A., Gluhak-Heinrich, J., Woodruff, K., Wittrant, Y., Cardenas, L., Roudier, M., & MacDougall, M. (2007). Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects. Archives of Oral Biology, 52(5), 432-443. https://doi.org/10.1016/j.archoralbio.2006.10.018

Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects. / Werner, S. Abboud; Gluhak-Heinrich, J.; Woodruff, K.; Wittrant, Y.; Cardenas, L.; Roudier, M.; MacDougall, M.

In: Archives of Oral Biology, Vol. 52, No. 5, 05.2007, p. 432-443.

Research output: Contribution to journalArticle

Werner, SA, Gluhak-Heinrich, J, Woodruff, K, Wittrant, Y, Cardenas, L, Roudier, M & MacDougall, M 2007, 'Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects', Archives of Oral Biology, vol. 52, no. 5, pp. 432-443. https://doi.org/10.1016/j.archoralbio.2006.10.018
Werner SA, Gluhak-Heinrich J, Woodruff K, Wittrant Y, Cardenas L, Roudier M et al. Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects. Archives of Oral Biology. 2007 May;52(5):432-443. https://doi.org/10.1016/j.archoralbio.2006.10.018
Werner, S. Abboud ; Gluhak-Heinrich, J. ; Woodruff, K. ; Wittrant, Y. ; Cardenas, L. ; Roudier, M. ; MacDougall, M. / Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects. In: Archives of Oral Biology. 2007 ; Vol. 52, No. 5. pp. 432-443.
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abstract = "Objective: The aim of this study was to characterize the tooth phenotype of CSF-1-deficient op/op mice and determine whether expression of csCSF-1 in these mice has a role in primary tooth matrix formation. Design: Ameloblasts and odontoblasts, isolated from wt/wt frozen sections using laser capture microdissection, were analysed for csCSF-1, sCSF-1 and CSF-1R mRNA by RT-PCR. Mandibles, excised from 8 days op/op and wt/wt littermates, were examined for tooth morphology as well as amelogenin and DMP1 expression using in situ hybridisation. op/opCS transgenic mice, expressing csCSF-1 in teeth and bone using the osteocalcin promoter, were generated. Skeletal X-rays and histomorphometry were performed; teeth were analysed for morphology and matrix proteins. Results: Normal dental cells in vivo express both CSF-1 isoforms and CSF-1R. Compared to wt/wt, op/op teeth prior to eruption showed altered dental cell morphology and dramatic reduction in DMP1 transcripts. op/opCS mice showed marked resolution of osteopetrosis, tooth eruption and teeth that resembled amelogenesis imperfecta-like phenotype. At 3 weeks, op/op teeth showed severe enamel and dentin defects and barely detectable amelogenin and DMP1. In op/opCS mice, DMP1 in odontoblasts increased to near normal and dentin morphology was restored; amelogenin also increased. Enamel integrity improved in op/opCS, although it was thinner than wt enamel. Conclusions: Results demonstrate that ameloblasts and odontoblasts are a source and potential target of CSF-1 isoforms in vivo. Expression of csCSF-1 within the tooth microenvironment is essential for normal tooth morphogenesis and may provide a mechanism for coordinating the process of tooth eruption with endogenous matrix formation.",
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AU - Woodruff, K.

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AU - Cardenas, L.

AU - Roudier, M.

AU - MacDougall, M.

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