OP-1 has more effect than mechanical signals in the control of tissue differentiation in healing rat tendons

Although osteogenic protein 1 (OP-1) is best known for its ability to induc e bone formation, it is a differentiation factor with diverse functions in the development of non-bony tissues. It is expressed in developing tendon. We therefore hypothesized that OP-1 might stimulate the differentiation of a tendon callus. Rat achilles tendons were transected and a collagen sponge with or without OP-1 was placed in the defect. OP-1 induced the formation of an ossicle, which reduced tendon strength at 2 weeks postoperatively. Ab olition of muscle force by tibial nerve transection or reducing load by for efoot amputation reduced tendon strength by almost half during the same per iod. Thus, traction forces are potent tendon-tissue inducers. OP-1 reduced the strength of denervated tendons even further, but the induced ossicles a ppeared similar to those in loaded tendons. Thus, both OP-1 and unloading i ndependently reduced tendon strength. in conclusion, the ability of OP-1 to induce bone was greater than the mechanical and environmental signals for a more traction-resistant tissue, indicating that signal proteins may have more direct or stronger effects than mechanical stimuli on tissue different iation. We also found that a single percutaneous injection of OP-1 reproduc ibly induced large amounts of bone in this setting, although it is generall y believed that BMPs always need to be inserted with a carrier.