An experimental model of fracture-healing was used to study the
production of types-I and II collagen by in situ hybridization. The
distribution of cartilage matrix in callus was determined by histochemical
staining. Messenger RNA (mRNA) for cartilage-specific type-II collagen was
detectable as early as the fifth day in a small number of cells that had
acquired a chondrocyte phenotype but that also contained type-I collagen
mRNA, suggesting an ongoing change in the expression of collagen genes. The
location of the first chondrocytes, which were adjacent to cortical bone,
suggested that they originated from cells that had derived from the
periosteum by differentiation. On the seventh day of callus formation, the
presence of both type-I and type-II collagen mRNA in chondrocytes of
expanding cartilage suggested that most growth occurred by differentiation
of mesenchymal cells and less by proliferation of differentiated
chondrocytes. Expansion continued until the tenth to fourteenth day, after
which the cartilage was replaced by woven bone. This was characterized by
the presence of osteoblasts that were active in the synthesis of type-I
collagen.