Lifelong accumulation of bone in mice lacking Pten in osteoblasts

Ximeng Liu, Katia J. Bruxvoort, Cassandra R. Zylstra, Jiarong Liu, Rachel Cichowski, Marie Claude Faugere, Mary L. Bouxsein, Chao Wan, Bart O. Williams, Thomas L. Clemens

Research output: Contribution to journalArticlepeer-review

141 Scopus citations


Bone formation is carried out by the osteoblast, a mesenchymal cell whose lifespan and activity are regulated by growth factor signaling networks. Growth factors activate phosphatidylinositol 3-kinase (PI3K), which enhances cell survival and antagonizes apoptosis through activation of Akt/PKB. This process is negatively regulated by the Pten phosphatase, which inhibits the activity of PI3K. In this study, we investigated the effects of Akt activation in bone in vivo by conditionally disrupting the Pten gene in osteoblasts by using Cre-mediated recombination. Mice deficient in Pten in osteoblasts were of normal size but demonstrated a dramatic and progressively increasing bone mineral density throughout life. In vitro osteoblasts lacking Pten differentiated more rapidly than controls and exhibited greatly reduced apoptosis in association with markedly increased levels of phosphorylated Akt and activation of signaling pathways downstream of activated Akt. These findings support a critical role for this tumor-suppressor gene in regulating osteoblast lifespan and likely explain the skeletal abnormalities in patients carrying germ-line mutations of PTEN.

Original languageEnglish
Pages (from-to)2259-2264
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 13 2007


  • Akt
  • Bone acquisition
  • High bone mass
  • Osteoblast survival

ASJC Scopus subject areas

  • General


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