THE EFFECT OF EXOGENOUS TRANSFORMING GROWTH-FACTOR-BETA-2 ON HEALING FRACTURES IN THE RABBIT

The effects of exogenous TGF-beta 2 on normally healing fractures were investigated to see if healing can be accelerated; TGF-beta 2 stimulate bone and cartilage formation on calvariae and long bones. TGF-beta 2 (60 or 600 ng) was injected around the developing callus of rabbit tibial fractures healing under stable, or unstable, mechanical conditions 4 days after fracture. The fractures were examined 5, 7, 10, and 14 days after fracture. A large amount of edema developed around the injection sites. The callus of fractures healing under stable mechanical conditions consists almost entirely of bone. The effects of 60-ng injections of TGF-beta 2 are minimal, but 600-ng doses lead to a small increase in the size of the callus. The callus of fractures healing under unstable mechanical conditions has a large area of cartilage over the fracture site with bone on each side, The effects of TGF-beta 2 on unstable fractures are to retard and reduce bone and cartilage formation in the callus. The overall size of the callus is not affected. In conclusion, TGF-beta 2 does not stimulate fracture healing under either stable, or unstable, mechanical conditions during the initial healing phase. It is argued that agents which stimulate bone formation can retard remodeling when treatment is extended into the remodeling phase of healing.