Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling

Zhong Jian Shen, Jie Hu, Aktar Ali, Johanne Pastor, Kazuhiro Shiizaki, Robert D. Blank, Makoto Kuro-o, James S. Malter

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Bone is constantly formed and resorbed throughout life by coordinated actions of osteoblasts and osteoclasts. However, the molecular mechanisms involved in osteoblast function remain incompletely understood. Here we show, for the first time, that the peptidyl-prolyl isomerase PIN1 controls the osteogenic activity of osteoblasts. Pin1 null mice exhibited an age-dependent decrease in bone mineral density and trabecular bone formation without alteration in cortical bone. Further analysis identified a defect in BMP signaling in Pin1 null osteoblasts but normal osteoclast function. PIN1 interacted with SMAD5 and was required for the expression by primary osteoblasts of osteoblast specific transcription factors (CBFA1 and OSX), ECM (collagen I and OCN) and the formation of bone nodules. Our results thus uncover a novel aspect of the molecular underpinning of osteoblast function and identify a new therapeutic target for bone diseases.

Original languageEnglish (US)
Article numbere63565
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 10 2013

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osteoblasts
Osteoblasts
Bone
bones
Bone and Bones
mice
osteoclasts
Osteoclasts
bone formation
Osteogenesis
Peptidylprolyl Isomerase
bone diseases
Military electronic countermeasures
isomerases
Bone Diseases
bone density
Bone Density
Minerals
collagen
Transcription Factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling. / Shen, Zhong Jian; Hu, Jie; Ali, Aktar; Pastor, Johanne; Shiizaki, Kazuhiro; Blank, Robert D.; Kuro-o, Makoto; Malter, James S.

In: PLoS One, Vol. 8, No. 5, e63565, 10.05.2013.

Research output: Contribution to journalArticle

Shen, Zhong Jian ; Hu, Jie ; Ali, Aktar ; Pastor, Johanne ; Shiizaki, Kazuhiro ; Blank, Robert D. ; Kuro-o, Makoto ; Malter, James S. / Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling. In: PLoS One. 2013 ; Vol. 8, No. 5.
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