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

Xiaojuan Wang, Shaoxi Liao, Erik Nelson, Robert Schmalzigaug, Robert F. Spurney, Farshid Guilak, Richard T. Premont, Diane Gesty-Palmer

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)407-412
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number2
DOIs
StatePublished - Aug 24 2012
Externally publishedYes

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Osteoclasts
Stem cells
Osteoblasts
Mesenchymal Stromal Cells
Scaffolds
Cell Differentiation
Bone
Bone Resorption
Proteins
G-Protein-Coupled Receptor Kinases
Receptor-Interacting Protein Serine-Threonine Kinases
Bone and Bones
Metabolic Bone Diseases
Adiposity
G-Protein-Coupled Receptors
Membrane structures
Cytoskeleton
Adipocytes
Osteogenesis
Bone Density

Keywords

  • Adipogenesis
  • Cytoskeleton
  • GIT2
  • Mesenchymal stem cell
  • Osteoblastogenesis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis. / Wang, Xiaojuan; Liao, Shaoxi; Nelson, Erik; Schmalzigaug, Robert; Spurney, Robert F.; Guilak, Farshid; Premont, Richard T.; Gesty-Palmer, Diane.

In: Biochemical and Biophysical Research Communications, Vol. 425, No. 2, 24.08.2012, p. 407-412.

Research output: Contribution to journalArticle

Wang, Xiaojuan ; Liao, Shaoxi ; Nelson, Erik ; Schmalzigaug, Robert ; Spurney, Robert F. ; Guilak, Farshid ; Premont, Richard T. ; Gesty-Palmer, Diane. / The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 425, No. 2. pp. 407-412.
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