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Impaired angiogenesis during fracture healing in GPCR kinase 2 interacting protein-1 (GIT1) knock out mice
- Source :
- PLoS ONE, Vol 9, Iss 2, p e89127 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- G protein coupled receptor kinase 2 (GRK2) interacting protein-1 (GIT1), is a scaffold protein that plays an important role in angiogenesis and osteoclast activity. We have previously demonstrated that GIT1 knockout (GIT1 KO) mice have impaired angiogenesis and dysregulated osteoclast podosome formation leading to a reduction in the bone resorbing ability of these cells. Since both angiogenesis and osteoclast-mediated bone remodeling are involved in the fracture healing process, we hypothesized that GIT1 participates in the normal progression of repair following bone injury. In the present study, comparison of fracture healing in wild type (WT) and GIT1 KO mice revealed altered healing in mice with loss of GIT1 function. Alcian blue staining of fracture callus indicated a persistence of cartilagenous matrix in day 21 callus samples from GIT1 KO mice which was temporally correlated with increased type 2 collagen immunostaining. GIT1 KO mice also showed a decrease in chondrocyte proliferation and apoptosis at days 7 and 14, as determined by PCNA and TUNEL staining. Vascular microcomputed tomography analysis of callus samples at days 7, 14 and 21 revealed decreased blood vessel volume, number, and connection density in GIT1 KO mice compared to WT controls. Correlating with this, VEGF-A, phospho-VEGFR2 and PECAM1 (CD31) were decreased in GIT1 KO mice, indicating reduced angiogenesis with loss of GIT1. Finally, calluses from GIT1 KO mice displayed a reduced number of tartrate resistant acid phosphatase-positive osteoclasts at days 14 and 21. Collectively, these results indicate that GIT1 is an important signaling participant in fracture healing, with gene ablation leading to reduced callus vascularity and reduced osteoclast number in the healing callus.
- Subjects :
- CD31
Anatomy and Physiology
Mouse
Angiogenesis
Gene Expression
Osteoclasts
lcsh:Medicine
Cell Cycle Proteins
Bone remodeling
Neovascularization
Mice
Molecular Cell Biology
Signaling in Cellular Processes
Bony Callus
lcsh:Science
Musculoskeletal System
Fracture Healing
Mice, Knockout
Multidisciplinary
Cell Death
GTPase-Activating Proteins
Animal Models
Signaling Cascades
medicine.anatomical_structure
Medicine
Intercellular Signaling Peptides and Proteins
Bone Remodeling
medicine.symptom
Research Article
Signal Transduction
medicine.medical_specialty
Neovascularization, Physiologic
Bone healing
Signaling Pathways
Bone and Bones
Chondrocyte
Model Organisms
Chondrocytes
Osteoclast
Internal medicine
medicine
Animals
Bone
Biology
lcsh:R
X-Ray Microtomography
Bone fracture
Phosphoproteins
medicine.disease
Mice, Inbred C57BL
Endocrinology
Immunology
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....186eea4d5364d318e0715e249bca8c69