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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Wang, X; Liao, S; Nelson, ER; Schmalzigaug, R; Spurney, RF; Guilak, F; Premont, RT; Gesty-Palmer, D

Published Date

  • August 24, 2012

Published In

Volume / Issue

  • 425 / 2

Start / End Page

  • 407 - 412

PubMed ID

  • 22846567

Pubmed Central ID

  • PMC3432571

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2012.07.111


  • eng

Conference Location

  • United States