The healing of fractures involving bone and articular cartilage poses significant clinical challenge and socioeconomic impact. Numerous factors may impair healing of fractures, particularly those involving joints. It is estimated that 10-15% of 6.5 million fractures occurring annually will not heal. The elderly are more severely impacted and have greater morbidity associated with resulting osteoarthritis. Gene transfer in combination with bone marrow-derived mesenchymal stem cells (BMDMSC), which are pluripotent, can allow for controlled production of transgene products at desired sites, however, studies have not evaluated healing in fractures involving joints. Our goal is to identify the roles of bone morphogenetic proteins (BMPs) in BMDMSC during fracture healing, using an adenoviral delivery system. We will create an articular fracture in the distal femur of mice, implant BMP gene-transfected BMDMSC, and measure molecular signals associated with the rate and integrity of fracture repair. We hypothesize that gene delivery of two different BMPs will result in accelerated healing of fractures, but by different mechanisms, confirmed by the production of unique cartilage- and bone-specific messages. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR050916-02
Application #
6908125
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Panagis, James S
Project Start
2004-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
2
Fiscal Year
2005
Total Cost
$65,327
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Zachos, Terri A; Bertone, Alicia L; Wassenaar, Peter A et al. (2007) Rodent models for the study of articular fracture healing. J Invest Surg 20:87-95
Zachos, Terri; Diggs, Alisha; Weisbrode, Steven et al. (2007) Mesenchymal stem cell-mediated gene delivery of bone morphogenetic protein-2 in an articular fracture model. Mol Ther 15:1543-50
Zachos, Terri A; Shields, Kathleen M; Bertone, Alicia L (2006) Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic proteins-2 or -6. J Orthop Res 24:1279-91