Current experimental approaches to bone development and healing have focused on the induction of bone formation by demineralized bone matrix (DBM). This induction is attributed to factors associated with DBM. These factors regulate various phases of osteogenesis by functioning in a cascade fashion. The mechanism of action for several of these factors has been elucidated, but little is known about the factor which regulate the proliferative phase of osteogeneic cells. In preliminary studies, we have identified a DBM-associated osteogenic cell mitogen which we have termed osteogenic growth factor (OsGF). The purpose of this project is to further purify and characterize OsGF. The osteogenic proliferative phase represents a major portion of bone healing time. The shortening of this phase could significantly reduce the time necessary for bone healing. Preliminary studies indicate: 1) OsGF implanted into murine bone defects can reduce the proliferative phase from 12 to 6 days. This 50% reduction in the proliferative phase results in a more rapid appearance of osteoids and osteoblasts. 2) OsGF addition to osteogenic cell cultures results in a four-fold increase in 3H-thymidine incorporation. 3) OsGF is a noncollagenous protein whose target cells appear to be restricted to cells derived from tissue that form bone under physiological and pathological conditions. 4) Both platelet-derived growth factor and fibronectin can serve as competence growth factors for OsGF. These studies indicate OsGF can shorten the proliferative phase and perhaps the overall bone healing time. The goal of the project is to purify OsGF from DBM and further characterize its biological and physical properties. To achieve this goal, cell cultures possessing osteogenic potential have been established and will serve as an appropriate target cell culture in which to monitor the purification of OsGF. The purified OsGF will be characterized in terms of its molecular weight, isoelectric point, and amino acid composition. Biological properties such as its mitogenesis will be investigated to determine OsGF's effects on bone healing. These studies will allow us to better understand the role of OsGF in the regulation of the proliferative phase of bone healing. This knowledge may contribute to future clinical use of factors such as OsGF in orthopedic, orthognathic, preprosthetic, and reconstructive surgery.
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