Biochemical characterization of a virus-induced osteosarcoma-like osseous lesion in vitro

Chondroprogenitor cells present in the apical and lateral parts of the mandibular condyle from neonatal mice differentiate towards the osteoblastic lineage and form bone within 7 days in culture. Infection of condylar explants with the FBR osteosarcoma virus (FBR MSV) results in the transformation of cells in the progenitor zone, previously identified as the target for the virus, and the formation of a transplantable osteosarcoma-like lesion. Morphological and biochemical changes in this system were investigated in the course of tumor development. Virus infection was followed by a significant increase in cell density and 3H-thymidine incorporation within the progenitor zone at the early stage of culture. In later stages, cell density and 3H-thymidine incorporation were lower than in control tissue. The 3H-thymidine labeling index gave similar results in infected and control tissues until day 7. Then, a significantly higher labeling index was found in the progenitor zone of infected condyles. At this stage, the proliferative effect of the virus even affected the cartilagenous core of the tissue. Quantitative alkaline phosphatase activity increased between day 3 and day 7 and was particularly high in the zone of infected cells. In addition, infected tissues consistently revealed a higher uptake of 45Ca, and deposition of the radioisotope along irregularly formed bone trabecules in the transformed tissue. The results suggest that there is an enhancement of tissue maturation following infection with the FBR osteosarcoma virus. Although biochemical investigations of whole condyles showed few differences in the total values of alkaline phosphatase activity, 3H-thymidine incorporation, DNA content, and 45Ca uptake, the histochemical assays revealed clear differences in the distributional pattern of these parameters within infected and control condyles.