Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by
$ \raise0.5ex\hbox{$ \raise0.5ex\hbox{ after 14 days, if loading is prevented. Exogenous GDFs stimulate tendon healing. This response is influenced by loading:
without loading, cartilage and bone formation is initiated. This implies BMP signaling is crucial during tendon healing and
influenced by mechanical loading. We therefore asked if mechanical loading influences the gene expression of the BMP signaling
system in intact and healing tendons, and how the BMP signaling system changes during healing. The genes were four BMPs (OP-1/BMP-7,
GDF-5/CDMP-1/BMP-14, GDF-6/CDMP-2/BMP-13, and GDF-7/CDMP-3/BMP-12), two receptors (BMPR1b and BMPR2), and the antagonists
follistatin and noggin. The Achilles tendon was transected in rats and left to heal. Half of the rats had one Achilles tendon
unloaded by injection of Botox in the calf muscles. Ten tendons were analyzed before transection and for each of four time
points. All genes except noggin were expressed at all time points, but followed different patterns during healing. Loading
strongly decreased the expression of follistatin, which could lead to increased signaling. The BMP system appears involved
in tendon maintenance and healing, and may respond to mechanical loading.
Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest,
patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. One or
more of the authors (PE, PA) received grants from the Swedish Research Council, the Strategic Research Program “Materials
in Medicine” by Östergötland County and the University of Linköping.
Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations
were conducted in conformity with ethical principles of research.