Osteoblast differentiation and migration are regulated by dynamin GTPase activity

Pierre P. Eleniste, Su Huang, Kornchanok Wayakanon, Heather W. Largura, Angela Bruzzaniti

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Bone formation is controlled by osteoblasts, but the signaling proteins that control osteoblast differentiation and function are still unclear. We examined if the dynamin GTPase, which is associated with actin remodeling and migration in other cells, plays a role in osteoblast differentiation and migration. Dynamin mRNA was expressed in primary osteoblasts throughout differentiation (0-21 days). However, alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation, was decreased in osteoblasts over-expressing dynamin. Conversely, ALP activity was increased following shRNA-mediated knockdown of dynamin and in osteoblasts treated with the dynamin inhibitor, dynasore. Dynasore also reduced c-fos and osterix expression, markers of early osteoblasts, suggesting a role for dynamin in pre-osteoblast to osteoblast differentiation. Since dynamin GTPase activity is regulated by tyrosine phosphorylation, we examined the mechanism of dynamin dephosphorylation in osteoblasts. Dynamin formed a protein complex with the tyrosine phosphatase PTP-PEST and inhibition of phosphatase activity increased the level of phosphorylated dynamin. Further, PTP-PEST blocked the Src-mediated increase in the phosphorylation and GTPase activity of wild-type dynamin but not the phosphorylation mutant dynY231F/Y597F. Although ALP activity was increased in osteoblasts expressing GTPase-defective dynK44A, and to a lesser extent dynY231F/Y597F, osteoblast migration was significantly inhibited by dynK44A and dynY231F/Y597F. These studies demonstrate a novel role for dynamin GTPase activity and phosphorylation in osteoblast differentiation and migration, which may be important for bone formation.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • Alkaline phosphatase
  • Dephosphorylation
  • PTP-PEST
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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