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

The expression of several collagens, cartilage proteoglycan core protein (aggrecan), and osteonectin was investigated during healing of standardized fractures of the mouse tibia. Total RNA was extracted from fracture calluses and normal bone, and analyzed by Northern hybridization using specific cDNA probes. Based on the predominant fibrillar collagen type expressed, three phases of fracture healing were observed. Type III collagen expression characteristic for the inflammatory stage increased 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 collagen and aggrecan expression coincided with Type II collagen expression during the chondrogenesis. The mRNA for Type X collagen, a marker for hypertrophic chondrocytes during endochondral ossification, occurred somewhat later than that of other cartilage-specific genes. Osteonectin mRNA was present throughout the healing process and peaked during rapid new bone growth. This study confirms that the pattern of gene expression in the murine system is similar to, but somewhat faster than, other species analyzed (rat, rabbit, human).