THE CELL AND MOLECULAR-BIOLOGY OF FRACTURE-HEALING

Fracture healing is a complex physiologic process that involves the co ordinated participation of several cell types. By using a reproducible model of experimental fracture healing in the rat, it is possible to elucidate the integrated cellular responses that signal the pathways a nd the role of the extracellular matrix components in orchestrating th e events of fracture healing. Histologic characterization of fracture healing shows that intramembranous ossification occurs under the perio steum within a few days after an injury. Events of endochondral ossifi cation occur adjacent to the fracture site and span a period of up to 28 days. Remodeling of the woven bone formed by intramembranous and en dochondral ossification proceeds for several weeks, Spatial and tempor al expression of genes for major collagens (Types I and II), minor fib rillar collagens (Types IV and XI), and several extracellular matrix c omponents (osteocalcin, osteonectin, osteopontin, fibronectin and CD44 ) are detected by in situ hybridization. Immunohistochemical studies s how that expression of proliferating cell nuclear antigen is both time and space dependent and differentially expressed in the callus tissue s formed by the intramembranous and endochondral processes. Chondrocyt es involved in endochondral ossification undergo apoptosis (programmed cell death), and early events in fracture healing may be initiated by the expression of early response genes such as c-fos, Additional char acterization and elucidation of fracture healing will lay the foundati on for subsequent studies aimed at identifying mechanisms for enhancin g skeletal repair.