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The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis.

Publication ,  Journal Article
Borton, AJ; Frederick, JP; Datto, MB; Wang, XF; Weinstein, RS
Published in: J Bone Miner Res
October 2001

Smad3 is a well-characterized intracellular effector of the transforming growth factor beta (TGF-beta) signaling pathway and was implicated recently in the potentiation of vitamin D receptor (VDR)-mediated signaling. Given that both TGF-beta and vitamin D are important regulators of bone remodeling, it is expected that Smad3 plays an integral role in normal maintenance of bone. However, the exact mechanisms by which Smad3 functions in bone remodeling are unknown. Here, we show that mice with targeted deletion of Smad3 are osteopenic with less cortical and cancellous bone compared with wild-type littermates. Decreases in bone mineral density (BMD) in Smad3 null mice reflect the inability of osteoblasts to balance osteoclast activity, although osteoclast numbers are normal and vitamin D mediated serum calcium homeostasis is maintained. The osteopenia of Smad3 null mice is attributed to a decreased rate of bone formation associated with increased osteocyte number and apoptosis. These findings are supported by studies with isolated primary osteoblasts that show TGF-beta can no longer inhibit the differentiation of osteoblasts in the absence of Smad3; yet, TGF-beta-stimulated proliferation remains intact. Together these data support a model that a loss of Smad3 increases the osteocyte fate of the osteoblast and decreases the duration of osteoblast function by shortening lifespan, ultimately resulting in osteopenia.

Duke Scholars

Published In

J Bone Miner Res

DOI

ISSN

0884-0431

Publication Date

October 2001

Volume

16

Issue

10

Start / End Page

1754 / 1764

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Trans-Activators
  • Smad3 Protein
  • Osteogenesis
  • Osteocytes
  • Osteoclasts
  • Osteoblasts
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
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ICMJE
MLA
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Borton, A. J., Frederick, J. P., Datto, M. B., Wang, X. F., & Weinstein, R. S. (2001). The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res, 16(10), 1754–1764. https://doi.org/10.1359/jbmr.2001.16.10.1754
Borton, A. J., J. P. Frederick, M. B. Datto, X. F. Wang, and R. S. Weinstein. “The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis.J Bone Miner Res 16, no. 10 (October 2001): 1754–64. https://doi.org/10.1359/jbmr.2001.16.10.1754.
Borton AJ, Frederick JP, Datto MB, Wang XF, Weinstein RS. The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res. 2001 Oct;16(10):1754–64.
Borton, A. J., et al. “The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis.J Bone Miner Res, vol. 16, no. 10, Oct. 2001, pp. 1754–64. Pubmed, doi:10.1359/jbmr.2001.16.10.1754.
Borton AJ, Frederick JP, Datto MB, Wang XF, Weinstein RS. The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res. 2001 Oct;16(10):1754–1764.
Journal cover image

Published In

J Bone Miner Res

DOI

ISSN

0884-0431

Publication Date

October 2001

Volume

16

Issue

10

Start / End Page

1754 / 1764

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Trans-Activators
  • Smad3 Protein
  • Osteogenesis
  • Osteocytes
  • Osteoclasts
  • Osteoblasts
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice