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. 2008 Jul;466(7):1592-7.
doi: 10.1007/s11999-008-0253-0. Epub 2008 Apr 18.

Mechanical load and BMP signaling during tendon repair: a role for follistatin?

Pernilla Eliasson  1 , Anna Fahlgren, Per Aspenberg
Affiliations

Mechanical load and BMP signaling during tendon repair: a role for follistatin?

Pernilla Eliasson et al. Clin Orthop Relat Res. 2008 Jul.

Abstract

Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by 3/4 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.

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Figures

Fig. 1
Fig. 1
This box plot shows the expression of the studied genes in intact tendons. The vertical axis shows the ratio to a housekeeping gene (18S rRNA). The horizontal axis shows loading status where loaded tendons (L) are light grey, and unloaded tendons (U) are darker grey. Loading had no major effect on any of the genes. N = 5 for each box.
Fig. 2
Fig. 2
This box plot shows the expression of the studied genes in all groups. The vertical axis shows the ratio to a housekeeping gene (18S rRNA). The horizontal axis shows time after tendon transection. L0 indicates intact loaded tendons. L3, L8, L14 and L21 indicate loaded healing tendons 3, 8, 14 and 21 days after tendon transection respectively. B0 indicates unloaded intact tendons analyzed 5 days after Botox injection. B3, B8, B14 and B21 indicate unloaded healing tendons 3, 8, 14 and 21 days after tendon transection respectively. Loaded tendons (L) are darker, and unloaded (U) are lighter. N = 5 for each box. During healing, loading decreased follistatin expression by more than half (p = 0.0001) and tended to slightly increase GDF-5. All genes showed changes during the time of the healing process (p = 0.0001 for each one). The expression of GDF-5 and GDF-7 was low during healing compared to normal tendons. GDF-7 was back at the level of intact tendons at 21 days, but GDF-5 remained low. OP-1 and GDF-6 showed a reciprocal pattern with high expression during early healing. Both receptors also showed a slight increase during healing, with a peak at 14 days and then a decrease.
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