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Background Joint contractures occur frequently after trauma or immobilization, but few reliable treatments are available. Extracorporeal shock wave therapy (ESWT) is often used for various musculoskeletal conditions, but whether it is effective for treating joint contractures and the mechanisms through which it might work for that condition remain unclear. @@@ Questions/purposes Using a rat model, we asked, does ESWT (1) inhibit the progression of knee contracture, (2) ameliorate histopathologic joint changes, and (3) improve serum and myofascial fibrosis-related factors? We also asked, (4) what is the possible mechanism by which ESWT inhibits knee contracture? @@@ Methods Thirty-two male Sprague-Dawley rats (12 weeks old andweighing 300 to 400 g) were randomly separated into two groups: control group (eight rats) and noncontrol group (24) in the first week. Rats in the control groupwere kept free in cages for 4 weeks, and the right lower limbs of the rats in the noncontrol group were immobilized in plaster for 4 weeks. ROM was then measured for each rat with or without 4 weeks of immobilization. After ROM measurement, rats in the noncontrol group were randomly separated into three groups: immobilization group (eight rats), remobilization group (eight rats), and remobilization with ESWT group (eight rats) at Week 4. Knee contracture was induced in rats by fixing the right knee with a plaster cast as in a previous study. The plaster cast was removed after 4 weeks; knee contracture was established when passive ROM was decreased and dysfunction such as abnormal gait occurred. Subsequently, rats with a remobilized joint contracture were treated with or without ESWT for 15 days (on Days 5, 10, and 15). The therapeutic effect was examined using ROM, joint diameter (as an indication of swelling), histopathologic changes, and the levels of fibrosis-related extracellularmatrix component factors (hyaluronic acid, serum procollagen peptide, and laminin). The effect ofESWTon fibrosis protein was also evaluated using immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blot. The expressions of factors in the TGF-b/SMADs pathway were also determined using Western blot and qPCR. @@@ Results ESWT mitigated immobilization-induced knee contracture in rats by improving ROM (immobilization versus remobilization with ESWT: 53 degrees +/- 8 degrees versus 32 degrees +/- 8 degrees [95% confidence interval 13 degrees to 30 degrees]; p < 0.001) and joint swelling (immobilization versus remobilization with ESWT: 8 +/- 0.8 cm versus 6 +/- 0.3 cm [95% CI 0.4 to 2.2 cm]; p = 0.01). Histopathologic features of remission were alleviated after ESWT (immobilization versus remobilization with ESWT: thickness of the knee space: 0.2 +/- 0.03 mm versus 0.6 +/- 0.01 mm [95% CI -0.49 to -0.33 mm]; p < 0.001. On Masson staining, the positive expression area, which indicates collagen fiber deposition, was 24% +/- 5% versus 9% 6 2% ([95% CI 10% to 21%]; p < 0.001). ESWT improved the serum fibrosis factors of hyaluronic acid, procollagen peptide, and laminin (immobilization versus remobilization with ESWT: hyaluronic acid: 412 +/- 32 versus 326 615 ng/mL [95% CI 29 to 144 ng/mL]; p = 0.003; serum procollagen peptide: 19 +/- 1 versus 12 +/- 1 ng/mL [95% CI 3 to 11 ng/mL]; p < 0.001; laminin: 624 +/- 78 versus 468 69 ng/mL [95% CI 81 to 231 ng/mL]; p = 0.006) and myofascial factors of alpha-SMA and Type I collagen associated with immobilization-induced contractures. @@@ Conclusion The findings suggest that ESWT improved joint contracture by inhibiting the TGF-beta 1/SMADs signaling pathway in rats.
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单位南方医科大学
