My research is currently focused in two areas of bone biology.

- Identification and characterization of subpopulations of cells during osteoprogenitor lineage differentiation.

Osteoblast precursors are recruited from a multipotential mesenchymal progenitor that can give rise to several differentiated cell phenotypes including fibroblasts, chondrocytes, adipocytes and osteoblasts. During this process of osteoblastic differentiation, an osteoprogenitor proliferates and undergoes a series of maturational steps before becoming a differentiated osteoblast. The purpose of our current work is to determine if the rat Col1a1 promoter fragments as well as the other promoters of connective tissue genes can be used to identify different subpopulations of cells within the osteoblast lineage. We have generated and characterized transgenic mice in which GFP expression is under the control of the 3.6 and 2.3 Col1a1 promoter fragments. Using this approach we have identified distinct populations of cells at different levels of maturations. Currently we are using FACS sorting to separate these populations and microarray analysis to assess their gene expression profile.

- Analyzing the performance of the osteoblast lineage in the osteogenesis imperfecta murine model (OIM).

Recent studies suggest that the pathophysiological basis of OI is a state of high bone turnover secondary to the accumulation of defective bone matrix as a consequence of the underlying molecular mutation within the Col1A1 or Col1A2 genes. This exaggerated process of bone remodeling may explain the clinical effectiveness of bisphosphonates in improving bone mass and decreasing fracture frequency. The aim of our project is to evaluate the ability of the osteoprogenitor lineage to produce fully differentiated osteoblasts in young and aged OIM mice. We are also testing the effects of agents that can modulate the rate of bone turnover in normal and OIM mice. This includes examination of the independent and combined effects of IGF-I (turnover stimulator) and bisphosphonates (turnover inhibitor).