Collaboration between Collagenous Matrix and Osteogenin Is Required for Bone Induction

There is a growing realization of the importance of collagenous extracellular matrix in growth, development, and diseases.' Repair and regeneration, in general, recapitulate the developmental stages of organogenesis, including osteogenesis. It is well known that bone has considerable potential for repair and regeneration. The detailed cellular and biochemical changes during collagenous bone matrix-induced endochondral bone formation have been investigated? The sequential development of cartilage, bone, and hematopoietic marrow is reminiscent of the cellular lineages in bone differentiation in epiphyseal growth plate and fracture repair. The matrix-induced bone formation system is a prototype for studies on the role of collagenous extracellular matrix in development and repair. The major phases of this developmental cascade are: chemotaxis and attachment of progenitor cells to collagenous matrix via fibronectin (days 1 -2), mitosis of mesenchymal stem cells (days 3-4), differentiation of cartilage (days 5-7), bone (days 10-11), and hematopoiesis (day 21). Progress in the characterization of bone-inductive protein, osteogenin, has been tardy in part due to the relatively insoluble nature of the bone matrix and the lack of rapid, reliable, and simple in vitro bioassays for bone induction. The dissociative extraction and solubilization of matrix components permitted an in vivo bioassay for new bone formation. The amount of bone formation is quantitated by the activity of alkaline phosphatase, an enzyme known to be intimately involved in ossification, and calcium content.2 Osteogenin has been purified to considerable extent by heparin affinity chromatography.' The role of the substratum in bone induction was investigated using insoluble collagenous matrix, hydroxyapatite, /3-tricalcium phosphate, polymethylmethacrylate, and glass beads. In these experiments partially purified osteogenin was reconstituted with the different substrata as described? The results (TABLE 1) demonstrated that there is a collaborative interaction between collagenous substratum and osteogenin to initiate bone formation. The delivery of bone induction factors in collagenous implants has been described.' The present results imply that collagenous matrix and osteogenin may be potentially useful in the realms of dentistry and orthopaedic surgery to initiate and promote bone repair.