Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1

Toru Nishiwaki, Toru Yamaguchi, Chen Zhao, Hitoshi Amano, Kurt D. Hankenson, Paul Bornstein, Yoshiaki Toyama, Koichi Matsuo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1 -/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. Introduction: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. Materials and Methods: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. Results: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1 -/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. Conclusions: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.

Original languageEnglish
Pages (from-to)596-604
Number of pages9
JournalJournal of Bone and Mineral Research
Volume21
Issue number4
DOIs
Publication statusPublished - 2006 Apr

Fingerprint

Thrombospondins
Osteosclerosis
Transgenic Mice
Thrombospondin 1
Bone Matrix
Osteoblasts
Ovariectomy
Bites and Stings
Bone and Bones
Proteins
Bone Remodeling
Transcription Factor AP-1
Transcription Factors
Western Blotting
Staining and Labeling
Phenotype
Polymerase Chain Reaction
thrombospondin 2

Keywords

  • AP-1
  • Bone matrix
  • Fra1
  • Osteoblast
  • Thrombospondin

ASJC Scopus subject areas

  • Surgery

Cite this

Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1. / Nishiwaki, Toru; Yamaguchi, Toru; Zhao, Chen; Amano, Hitoshi; Hankenson, Kurt D.; Bornstein, Paul; Toyama, Yoshiaki; Matsuo, Koichi.

In: Journal of Bone and Mineral Research, Vol. 21, No. 4, 04.2006, p. 596-604.

Research output: Contribution to journalArticle

Nishiwaki, T, Yamaguchi, T, Zhao, C, Amano, H, Hankenson, KD, Bornstein, P, Toyama, Y & Matsuo, K 2006, 'Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1', Journal of Bone and Mineral Research, vol. 21, no. 4, pp. 596-604. https://doi.org/10.1359/jbmr.051216
Nishiwaki, Toru ; Yamaguchi, Toru ; Zhao, Chen ; Amano, Hitoshi ; Hankenson, Kurt D. ; Bornstein, Paul ; Toyama, Yoshiaki ; Matsuo, Koichi. / Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1. In: Journal of Bone and Mineral Research. 2006 ; Vol. 21, No. 4. pp. 596-604.
@article{66564d959e654b9fbb9163b550be5d5a,
title = "Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1",
abstract = "Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1 -/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. Introduction: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. Materials and Methods: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. Results: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1 -/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. Conclusions: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.",
keywords = "AP-1, Bone matrix, Fra1, Osteoblast, Thrombospondin",
author = "Toru Nishiwaki and Toru Yamaguchi and Chen Zhao and Hitoshi Amano and Hankenson, {Kurt D.} and Paul Bornstein and Yoshiaki Toyama and Koichi Matsuo",
year = "2006",
month = "4",
doi = "10.1359/jbmr.051216",
language = "English",
volume = "21",
pages = "596--604",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1

AU - Nishiwaki, Toru

AU - Yamaguchi, Toru

AU - Zhao, Chen

AU - Amano, Hitoshi

AU - Hankenson, Kurt D.

AU - Bornstein, Paul

AU - Toyama, Yoshiaki

AU - Matsuo, Koichi

PY - 2006/4

Y1 - 2006/4

N2 - Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1 -/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. Introduction: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. Materials and Methods: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. Results: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1 -/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. Conclusions: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.

AB - Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1 -/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. Introduction: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. Materials and Methods: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. Results: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1 -/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. Conclusions: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.

KW - AP-1

KW - Bone matrix

KW - Fra1

KW - Osteoblast

KW - Thrombospondin

UR - http://www.scopus.com/inward/record.url?scp=33645350874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645350874&partnerID=8YFLogxK

U2 - 10.1359/jbmr.051216

DO - 10.1359/jbmr.051216

M3 - Article

VL - 21

SP - 596

EP - 604

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 4

ER -