Mechanical stress plays an important role in preserving the integrity of bone and ligament. Stress shielding reduces mechanical load on bone or tendons, resulting in tissue degradation. Previous studies showed that deterioration of the tendon structure during stress shielding is associated with elevated expression of tumor necrosis factor (TNF)-α. This study examined the therapeutic potential of the TNF inhibitor etanercept in preventing morphologic deterioration of the Achilles tendon after stress shielding. Rats (N=48) were exposed to stress shielding of the left Achilles tendon and treated with etanercept or phosphate-buffered saline for 2 or 4 weeks. The right Achilles tendons were used as controls. After 2 or 4 weeks, stress-shielded tendons appeared less smooth than control tendons, and the stress-shielded tendons formed adhesions with surrounding tissues. Transmission electron microscopy also showed disarray of the collagen fibrils and a significant increase in the number of small-diameter collagen fibrils. These changes were associated with increased expression of TNF-α, matrix metalloproteinase (MMP)-13, MMP-3, collagen I, and collagen III. Treatment with 2 weeks of etanercept injection reduced morphologic changes in collagen organization and structure induced by stress shielding. Etanercept treatment also attenuated upregulation of MMP-13, MMP-3, and collagen III levels. However, no significant difference was observed between the etanercept group and the phosphate-buffered saline group after 4 weeks of treatment. The current findings show that TNF-α inhibition can protect against the early stages of tendon tissue remodeling induced by stress shielding, but additional interventions may be necessary to prevent tendon degeneration with long-term stress shielding. [Orthopedics. 2017; 40(1):49-55.].
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