Bioactive Factors


     Demineralized bone matrix (DBM) is active human bone that has been processed, ground and demineralized to form a uniform powder that contains the bone’s native osteoconductive and osteoinductive processes. Clinicians have used DBM to recruit pluripotent cells to enhance healing and provide space filling within bony defects. Some bioactive factors that are present in DBM include morphogens, growth factors and cytokines, all of which promote differentiation into both osteo- and chondrogenic lineages. Morphogens that have been isolated from active DBM include BMPs 2, 4 and 7 and it has always been assumed that these proteins account for the majority of DBM osteoinductivity. To date, however, few studies have compared DBM with purified BMPs.

     Traditionally, DBM bioactivity has been assayed via the production of ectopic bone upon explantation of DBM in muscle with outcomes analyzed histologically. Our goal is to develop a predictive in vitro assay for the in vivo bioactivity of DBM. Cells from a mesenchymal lineage are treated with DBM and changes in gene expression are monitored. Specifically, we wish to know the extent to which DBM-induced differentiation is due to direct contact with the powder itself or influence from soluble factors released into the aqueous environment. Additionally, we compare the molecular mechanisms of osteogenic differentiation in mesenchymal cells treated with DBM and BMP 2, respectively. Using our in vitro protocol, we will be able to delineate DBM molecular mechanisms and identify early markers of DBM-induced osteogenic differentiation.


     Parathyroid hormone (PTH) is the first FDA approved systemic anabolic factor that has been shown to increase bone mass in osteoporotic patients. There is an increasing awareness that the anabolic activity of PTH may have additional applications in Orthopaedics. Several studies have recently reported on the enhanced healing of fractures treated with systemically administered PTH. However, the molecular mechanisms by which either enhanced healing or regain of bone mass in osteoporotic conditions is achieved remain elusive. The majority of research to date has focused on the role of PTH in modulating osteoblast function in the context of coupled remodeling. While this may be an important component of PTH mediated enhanced bone formation, alternate mechanisms may exist in fracture repair that occurs through an endochondral process dependent on early chondrogenic events. In order to define the stages of fracture repair enhanced by PTH treatment we are investigating the tissue, cellular, and molecular effects of PTH treatment (40 micrograms/kilograms, PTH 1-34) during bone healing in a murine femoral fracture model.