Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts

Chaozhe Yang, Lei Yang, Mei Wan, Xu Cao

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Different working modes were proposed to explain how bone morphogenetic protein (BMP) type I and II receptors are involved in Smad phosphorylation cascades. In addition, both parathyroid hormone (PTH) and Wnts are also known to regulate phosphorylation of Smads. Here we established a mouse model in which a C-terminal truncated BMP type II receptor (BMPRII) is expressed specifically in osteoblasts as a dominant negative form in the BMP/Smad signaling pathway. Smad1/5/8 phosphorylation levels were reduced in bone marrow stromal cells from the transgenic mice. The sizes of embryos were smaller, and the mineralization of calvarial bones and lumbar vertebrae were delayed in mice expressing the transgene. In adult transgenic mice, total bone volume was reduced with no significant changes observed in cortical bone. Thus, osteoblast-targeted expression of dominant negative BMPRII leads to inhibited Smad1 phosphorylation, delayed skeletal development, and decreased bone formation in the adult mice. This study provides an in vivo tool to study the role of BMPRII in BMP/Smad signaling and the regulation of this pathway by PTH and Wnts.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Pages286-291
Number of pages6
Volume1192
DOIs
StatePublished - Mar 2010

Publication series

NameAnnals of the New York Academy of Sciences
Volume1192
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Type II Bone Morphogenetic Protein Receptors
Osteoblasts
Phosphorylation
Bone
Bone Morphogenetic Proteins
Parathyroid Hormone
Transgenic Mice
Type I Bone Morphogenetic Protein Receptors
Physiologic Calcification
Lumbar Vertebrae
Mesenchymal Stromal Cells
Transgenes
Osteogenesis
Embryonic Structures
Bone and Bones

Keywords

  • BMP type II receptor
  • Bone formation
  • Osteoblasts
  • Transgenic mouse model

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yang, C., Yang, L., Wan, M., & Cao, X. (2010). Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts. In Annals of the New York Academy of Sciences (Vol. 1192, pp. 286-291). (Annals of the New York Academy of Sciences; Vol. 1192). https://doi.org/10.1111/j.1749-6632.2009.05248.x

Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts. / Yang, Chaozhe; Yang, Lei; Wan, Mei; Cao, Xu.

Annals of the New York Academy of Sciences. Vol. 1192 2010. p. 286-291 (Annals of the New York Academy of Sciences; Vol. 1192).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Yang, C, Yang, L, Wan, M & Cao, X 2010, Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts. in Annals of the New York Academy of Sciences. vol. 1192, Annals of the New York Academy of Sciences, vol. 1192, pp. 286-291. https://doi.org/10.1111/j.1749-6632.2009.05248.x
Yang C, Yang L, Wan M, Cao X. Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts. In Annals of the New York Academy of Sciences. Vol. 1192. 2010. p. 286-291. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2009.05248.x
Yang, Chaozhe ; Yang, Lei ; Wan, Mei ; Cao, Xu. / Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts. Annals of the New York Academy of Sciences. Vol. 1192 2010. pp. 286-291 (Annals of the New York Academy of Sciences).
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