Optimization of Fibroblast Growth Factor-1 as an Anabolic Agent for Osteoporosis
Abstract
The long term goal of this research program is to develop fibroblast growth factor-1 through rational protein engineering into a potent and specific anabolic agent for the treatment of osteoporosis and fracture repair. The specific aims of this research plan are: 1) To evaluate the effects of existing mutant forms of FGF-1 on bone cells in vitro, on bone formation in vivo and to assess their toxicological or undesirable effects. 2) To generate additional FGF-1 mutants or chimeric proteins that are likely to exhibit enhanced anabolic activity on bone with reduced toxicity. Significant progress was made towards these goals during the course of support for this program. A number of different FGF-1 variants were generated and their in vitro and in vivo efficacy tested. Among these Argl36Lys mutant was the most osteoinductive followed by Cys-free > FGF-1 > FGF-HBGAM chimera. Furthermore, we demonstrated that injection of FGF-1 directly into the marrow cavity induces new bone formation suggesting the possibility of local delivery as a strategy to specifically increase the density of bone that are at risk of fracture. Finally, we can show that FGF can enhance the osteogenic differentiation of marrow stromal cells suspended in fibrin sealant, which serves as a manipulable delivery vehicle for both cells and growth factor(s).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADB285846
Entities
People
- Wilson H. Burgess
Organizations
- American Red Cross