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GIT1 is critical for formation of the CD31hiEmcnhi vessel subtype in coupling osteogenesis with angiogenesis via modulating preosteoclasts secretion of PDGF-BB
- Source :
- Bone. 122:218-230
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- G protein-coupled receptor kinase 2 interacting protein-1 (GIT1) is a scaffold protein that plays a vital role in bone modeling and remodeling during osteogenesis coupled with angiogenesis. Recent studies have shown that a specialized subset of vascular endothelium strongly positive for CD31 and Endomucin (CD31hiEmcnhi) is coupled with anabolic bone formation. Based on our previous finding that GIT1 knockout (GIT1 KO) mice have impaired angiogenesis and bone formation, we hypothesized that GIT1 affects formation of the CD31hiEmcnhi vessel subtype. In the current study, GIT1 knockout (GIT1 KO) mice displayed a significant decrease in trabecular bone mass and CD31hiEmcnhi vessel number, compared to their wild-type counterparts. In the fracture healing mouse model, GIT1 KO mice contained a lower number of CD31hiEmcnhi vessels in fracture callus at days 7 and 14. However, no significant differences in the number of preosteoclasts in bone marrow, trabecular bone and callus in GIT1 KO mice were observed, compared with wild-type mice. Notably, concentrations of serum platelet-derived growth factor-BB(PDGF-BB) secreted by preosteoclasts associated with CD31hiEmcnhi vessel formation were lower in GIT1 KO mice. In addition, PDGF-BB-associated expression of phosphorylated extracellular signal-regulated kinase- 1/2 (ERK1/2) and specificity protein 1 (SP1) was significantly decreased in preosteoclasts of GIT1 KO mice. These results collectively suggest that GIT1 is a critical participant in formation of the CD31hiEmcnhi vessel subtype, highlighting a novel biologic function of this scaffold protein in preosteoclasts.
- Subjects :
- 0301 basic medicine
CD31
Scaffold protein
Histology
biology
Physiology
Angiogenesis
Chemistry
Kinase
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Bone healing
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
biology.protein
medicine
Bone marrow
Receptor
Platelet-derived growth factor receptor
Subjects
Details
- ISSN :
- 87563282
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Bone
- Accession number :
- edsair.doi...........7a9a58c6b9e9bb8eb86975f0a85885ce