The biological events that follow
a bone fracture constitute a tissue regenerative process, whereby
the injured tissue is ultimately replaced by bone. This regenerative
process is characterized by a number of complex, interdependent
stages, which involve cellular and biochemical events that orchestrate
the proliferation and differentiation of cells, as well as the production
of many proteins. Ultimately, the intricate process of fracture
repair is regulated by the differential expression of specific genes,
occurring at the appropriate time and place. Whereas the biomechanics,
histology, and biochemistry of the different steps involved in fracture
healing have been studied extensively, very few reports focus on
the molecular events. It is precisely for this reason that the molecular
events are of interest to us. We believe that differential gene
expression underlies the essence of the bone repair process, and
therefore identification of fracture repair-specific genes (both
novel and known) will unveil the clinical key to accelerate the
healing of fractures. During our first funding period (1997-1998),
we identified and isolated a number of differentially expressed
genes (cDNAs) from fracture calluses, two of which are novel and
have been fully cloned. The goal of the proposed study is to continue
identifying and isolating fracture repair-specific genes using a
more direct approach. This work will continue to contribute to our
understanding of the molecular mechanisms involved in the healing
process and enhance our ability to treat fractures. |