REGULATION OF EXTRACELLULAR-MATRIX GENES DURING FRACTURE-HEALING IN MICE

The expression of several collagens, cartilage proteoglycan core prote in (aggrecan), and osteonectin was investigated during healing of stan dardized fractures of the mouse tibia. Total RNA was extracted from fr acture calluses and normal bone, and analyzed by Northern hybridizatio n using specific cDNA probes. Based on the predominant fibrillar colla gen type expressed, three phases of fracture healing were observed. Ty pe III collagen expression characteristic for the inflammatory stage i ncreased first, followed by Type II collagen expression indicative of the cartilaginous reparative phase, and by Type I collagen production, characteristic for the ossification and remodelling stages. Type IX c ollagen and aggrecan expression coincided with Type II collagen expres sion during the chondrogenesis. The mRNA for Type X collagen, a marker for hypertrophic chondrocytes during endochondral ossification, occur red somewhat later than that of other cartilage-specific genes. Osteon ectin mRNA was present throughout the healing process and peaked durin g rapid new bone growth. This study confirms that the pattern of gene expression in the murine system is similar to, but somewhat faster tha n, other species analyzed (rat, rabbit, human).