Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation

Ming Zhao, Stephen E Harris, Diane Horn, Zhaopo Geng, Riko Nishimura, Gregory R. Mundy, Di Chen

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.

Original languageEnglish (US)
Pages (from-to)1049-1060
Number of pages12
JournalJournal of Cell Biology
Volume157
Issue number6
DOIs
StatePublished - Jun 10 2002
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein Receptors
Osteoblasts
Osteogenesis
Transgenic Mice
Bone Morphogenetic Proteins
Type I Bone Morphogenetic Protein Receptors
Bone and Bones
Bone Matrix
Protein-Serine-Threonine Kinases
Bone Development
Osteoclasts
Collagen Type I
Bone Density
Phenotype

Keywords

  • BMP
  • Bone formation
  • Osteoblast differentiation
  • Receptor
  • Transgenic mice

ASJC Scopus subject areas

  • Cell Biology

Cite this

Zhao, M., Harris, S. E., Horn, D., Geng, Z., Nishimura, R., Mundy, G. R., & Chen, D. (2002). Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. Journal of Cell Biology, 157(6), 1049-1060. https://doi.org/10.1083/jcb.200109012

Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. / Zhao, Ming; Harris, Stephen E; Horn, Diane; Geng, Zhaopo; Nishimura, Riko; Mundy, Gregory R.; Chen, Di.

In: Journal of Cell Biology, Vol. 157, No. 6, 10.06.2002, p. 1049-1060.

Research output: Contribution to journalArticle

Zhao, M, Harris, SE, Horn, D, Geng, Z, Nishimura, R, Mundy, GR & Chen, D 2002, 'Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation', Journal of Cell Biology, vol. 157, no. 6, pp. 1049-1060. https://doi.org/10.1083/jcb.200109012
Zhao, Ming ; Harris, Stephen E ; Horn, Diane ; Geng, Zhaopo ; Nishimura, Riko ; Mundy, Gregory R. ; Chen, Di. / Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. In: Journal of Cell Biology. 2002 ; Vol. 157, No. 6. pp. 1049-1060.
@article{4ad775a70f8345029ec903028ccb497b,
title = "Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation",
abstract = "Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.",
keywords = "BMP, Bone formation, Osteoblast differentiation, Receptor, Transgenic mice",
author = "Ming Zhao and Harris, {Stephen E} and Diane Horn and Zhaopo Geng and Riko Nishimura and Mundy, {Gregory R.} and Di Chen",
year = "2002",
month = "6",
day = "10",
doi = "10.1083/jcb.200109012",
language = "English (US)",
volume = "157",
pages = "1049--1060",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation

AU - Zhao, Ming

AU - Harris, Stephen E

AU - Horn, Diane

AU - Geng, Zhaopo

AU - Nishimura, Riko

AU - Mundy, Gregory R.

AU - Chen, Di

PY - 2002/6/10

Y1 - 2002/6/10

N2 - Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.

AB - Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.

KW - BMP

KW - Bone formation

KW - Osteoblast differentiation

KW - Receptor

KW - Transgenic mice

UR - http://www.scopus.com/inward/record.url?scp=0037054548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037054548&partnerID=8YFLogxK

U2 - 10.1083/jcb.200109012

DO - 10.1083/jcb.200109012

M3 - Article

C2 - 12058020

AN - SCOPUS:0037054548

VL - 157

SP - 1049

EP - 1060

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -