In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development

S. J. Choi, G. David Roodman, J. Q. Feng, I. S. Song, K. Amin, P. S. Hart, J. T. Wright, N. Haruyama, T. C. Hart

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Distal-less 3 (DLX3) gene mutations are etiologic for Tricho-Dento-Osseous syndrome. To investigate the in vivo impact of mutant DLX3 on bone development, we established transgenic (TG) mice expressing the c.571_574delGGGG DLX-3 gene mutation (MT-DLX3) driven by a mouse 2.3 Col1A1 promoter. Microcomputed tomographic analyses demonstrated markedly increased trabecular bone volume and bone mineral density in femora from TG mice. In ex vivo experiments, TG mice showed enhanced differentiation of bone marrow stromal cells to osteoblasts and increased expression levels of bone formation markers. However, TG mice did not show enhanced dynamic bone formation rates in in vivo fluorochrome double labeling experiments. Osteoclastic differentiation capacities of bone marrow monocytes were reduced in TG mice in the presence of osteoclastogenic factors and the numbers of TRAP(+) osteoclasts on distal metaphyseal trabecular bone surfaces were significantly decreased. TRACP 5b and CTX serum levels were significantly decreased in TG mice, while IFN-γ levels were significantly increased. These data demonstrate that increased levels of IFN-γ decrease osteoclast bone resorption activities, contributing to the enhanced trabecular bone volume and mineral density in these TG mice. These data suggest a novel role for this DLX-3 mutation in osteoclast differentiation and bone resorption.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalDevelopmental Biology
Volume325
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Fingerprint

Sequence Deletion
Bone Development
Transgenic Mice
Genes
Osteoclasts
Bone Resorption
Osteogenesis
Bone Density
Mutation
Osteoblasts
Mesenchymal Stromal Cells
Fluorescent Dyes
Femur
Monocytes
Bone Marrow
Bone and Bones
Serum
Cancellous Bone

Keywords

  • Bone mineralization
  • DLX3
  • Interferon-gamma
  • Osteoclast
  • Rodent
  • Transgenic mice

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Choi, S. J., Roodman, G. D., Feng, J. Q., Song, I. S., Amin, K., Hart, P. S., ... Hart, T. C. (2009). In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development. Developmental Biology, 325(1), 129-137. https://doi.org/10.1016/j.ydbio.2008.10.014

In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development. / Choi, S. J.; Roodman, G. David; Feng, J. Q.; Song, I. S.; Amin, K.; Hart, P. S.; Wright, J. T.; Haruyama, N.; Hart, T. C.

In: Developmental Biology, Vol. 325, No. 1, 01.01.2009, p. 129-137.

Research output: Contribution to journalArticle

Choi, SJ, Roodman, GD, Feng, JQ, Song, IS, Amin, K, Hart, PS, Wright, JT, Haruyama, N & Hart, TC 2009, 'In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development', Developmental Biology, vol. 325, no. 1, pp. 129-137. https://doi.org/10.1016/j.ydbio.2008.10.014
Choi, S. J. ; Roodman, G. David ; Feng, J. Q. ; Song, I. S. ; Amin, K. ; Hart, P. S. ; Wright, J. T. ; Haruyama, N. ; Hart, T. C. / In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development. In: Developmental Biology. 2009 ; Vol. 325, No. 1. pp. 129-137.
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