GENE-EXPRESSION DURING BONE REPAIR

Detailed understanding of the basic events in fracture healing constit utes a foundation for the development of new approaches to stimulate b one healing. Since the fracture healing process repeats, in an adult o rganism, several stages of skeletal growth in the same temporal order, it offers an interesting model for developmental regulation of cellul ar phenotypes and tissue-specific genes. Molecular biology has introdu ced new methods to study the regulatory phenomena during the process o f fracture repair. Gene technology has also produced purified growth f actors for research, which will help to understand their roles in frac ture healing. This review summarizes data on the regulation of genes c oding for extracellular matrix components and growth regulatory molecu les during fracture healing. The information available focuses on the sequential expression of genes coding for collagens, proteoglycans, an d some other matrix proteins during secondary (callus) healing. The te mporal and spatial appearance of the different connective tissue compo nents, mesenchyme, cartilage, and bone, are closely linked to the expr ession of genes coding for their characteristic constituents. Members of the transforming growth factor-beta superfamily, such as the bone m orphogenetic proteins (BMP), are currently the most interesting ones a mong the factors that regulate chondrogenesis and osteogenesis. In the coming years, the availability of new cloned probes combined with sen sitive analytical methods, as reviewed here, will add greatly to our u nderstanding of the various aspects of gene expression during bone rep air. This information should provide answers to some of the unresolved questions in fracture callus development.