Associate Provost for Research Boston University Medical Campus
NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases	Research Resources

Abstract

Abstract: One of the major complications associated with skeletal healing after surgical treatment or traumatic injury is caused by the diabetic condition. Osseous healing in diabetic animals represents one of the most clinically relevant model systems to study how systemic metabolic dysregulation affects skeletal tissues. Despite this, surprisingly little is known about the mechanisms by which diabetes affects osseous repair. The hypothesis of this project is that diabetes impairs bone formation during skeletal repair by altering angiogenesis and inhibiting the expression of genes that regulate osteoblast differentiation. Specific changes in the molecular mechanisms that control repair including alterations in immune cell function, inflammation and the signals associated with neovascularization, osteoblast differentiation and matrix turnover will be investigated in control and diabetic mice. Comparison to normal repair and repair that takes place in animals in which the metabolic dysfunction has been corrected through insulin treatment will be assessed. Thus, these studies will use histologic, cellular and molecular techniques to dissect the role of vascularization, altered BMP function and the underlying transcriptional regulation of osteoblast differentiation as mechanisms by which diabetes interferes with skeletal repair. In addition, the utilization of a genomics core will provide the means to identify novel pathways through which diabetes affects bone formation during repair.

Thesaurus Terms:
angiogenesis, biological signal transduction, bone fracture, bone regeneration, chondrocyte, protein structure function, vascular endothelial growth factor
cell differentiation, diabetes mellitus, inhibitor /antagonist
genetically modified animal, laboratory mouse

Institution:	BOSTON UNIVERSITY MEDICAL CAMPUS
	715 ALBANY ST, 560
	BOSTON, MA 021182394
Fiscal Year:	2006
Department:
Project Start:
Project End:
ICD:	NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
IRG:	ZAR1