Role of PAPP-A in Skeletal Development and Remodeling.

The IGFs are important for the structure and function of the skeleton through their potent anabolic effects on bone cell proliferation, differentiation, survival and matrix protein synthesis. Using the PAPP-A knock-out mouse model and well-characterized mouse and human bone cell cultures, we are testing the central hypothesis that PAPP-A, through its regulation of local IGF bioavailability, is a key regulator of bone formation. This work includes dynamic and static bone histomorphometry, bone mineral density measurements, and mechanical strength testing, as well as, gene expression studies. The information will provide new insights into the physiology and pathophysiology of the IGF system in bone that could lead to novel approaches for treatment of disorders of bone formation.