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The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis.

Publication ,  Journal Article
Wang, X; Liao, S; Nelson, ER; Schmalzigaug, R; Spurney, RF; Guilak, F; Premont, RT; Gesty-Palmer, D
Published in: Biochem Biophys Res Commun
August 24, 2012

G protein-coupled receptor kinase interacting protein 2 (GIT2) is a signaling scaffold protein involved in the regulation of cytoskeletal structure, membrane trafficking, and G protein-coupled receptor internalization. Since dynamic cytoskeletal reorganization plays key roles both in osteoblast differentiation and in the maintenance of osteoclast polarity during bone resorption, we hypothesized that skeletal physiology would be altered in GIT2(-/-) mice. We found that adult GIT2(-/-) mice have decreased bone mineral density and bone volume in both the trabecular and cortical compartments. This osteopenia was associated with decreased numbers of mature osteoblasts, diminished osteoblastic activity, and increased marrow adiposity, suggesting a defect in osteoblast maturation. In vitro, mesenchymal stem cells derived from GIT2(-/-) mice exhibited impaired differentiation into osteoblasts and increased adipocyte differentiation, consistent with a role for GIT2 in mesenchymal stem cell fate determination. Despite elevated osteoclast inducing cytokines and osteoclast numbers, GIT2(-/-) mice also exhibit impaired bone resorption, consistent with a further role for GIT2 in regulating osteoclast function. Collectively, these findings underscore the importance of the cytoskeleton in both osteoblast and osteoclast function and demonstrate that GIT2 plays essential roles in skeletal metabolism, affecting both bone formation and bone resorption in vivo.

Duke Scholars

Published In

Biochem Biophys Res Commun

DOI

EISSN

1090-2104

Publication Date

August 24, 2012

Volume

425

Issue

2

Start / End Page

407 / 412

Location

United States

Related Subject Headings

  • Phosphoproteins
  • Osteogenesis
  • Osteoblasts
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Mesenchymal Stem Cells
  • Male
  • Intercellular Signaling Peptides and Proteins
  • GTPase-Activating Proteins
 

Citation

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Wang, X., Liao, S., Nelson, E. R., Schmalzigaug, R., Spurney, R. F., Guilak, F., … Gesty-Palmer, D. (2012). The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis. Biochem Biophys Res Commun, 425(2), 407–412. https://doi.org/10.1016/j.bbrc.2012.07.111
Wang, Xiaojuan, Shaoxi Liao, Erik R. Nelson, Robert Schmalzigaug, Robert F. Spurney, Farshid Guilak, Richard T. Premont, and Diane Gesty-Palmer. “The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis.Biochem Biophys Res Commun 425, no. 2 (August 24, 2012): 407–12. https://doi.org/10.1016/j.bbrc.2012.07.111.
Wang X, Liao S, Nelson ER, Schmalzigaug R, Spurney RF, Guilak F, et al. The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis. Biochem Biophys Res Commun. 2012 Aug 24;425(2):407–12.
Wang, Xiaojuan, et al. “The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis.Biochem Biophys Res Commun, vol. 425, no. 2, Aug. 2012, pp. 407–12. Pubmed, doi:10.1016/j.bbrc.2012.07.111.
Wang X, Liao S, Nelson ER, Schmalzigaug R, Spurney RF, Guilak F, Premont RT, Gesty-Palmer D. The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis. Biochem Biophys Res Commun. 2012 Aug 24;425(2):407–412.
Journal cover image

Published In

Biochem Biophys Res Commun

DOI

EISSN

1090-2104

Publication Date

August 24, 2012

Volume

425

Issue

2

Start / End Page

407 / 412

Location

United States

Related Subject Headings

  • Phosphoproteins
  • Osteogenesis
  • Osteoblasts
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Mesenchymal Stem Cells
  • Male
  • Intercellular Signaling Peptides and Proteins
  • GTPase-Activating Proteins