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 induce 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. Abolition of muscle force by tibial nerve transection or reducing load by forefoot amputation reduced tendon strength by almost half during the same period. Thus, traction forces are potent tendon-tissue inducers. OP-1 reduced the strength of denervated tendons even further, but the induced ossicles appeared similar to those in loaded tendons. Thus, both OP-1 and unloading independently reduced tendon strength. In conclusion, the ability of OP-1 to induce bone was greater that 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 differentiation. We also found that a single percutaneous injection of OP-1 reproducibly induced large amounts of bone in this setting, although it is generally believed that BMPs always need to be inserted with a carrier.