Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, 89081 Ulm, Germany.
Institute of Orthopedic Research and Biomechanics, University Medical Center Ulm, Helmholtzstraße 14, 89081 Ulm, Germany.
Bone. 2018 May;110:11-20. doi: 10.1016/j.bone.2018.01.017. Epub 2018 Feb 3.
Mechanostimulation by low-magnitude high frequency vibration (LMHFV) has been shown to provoke anabolic effects on the intact skeleton in both mice and humans. However, experimental studies revealed that, during bone fracture healing, the effect of whole-body vibration is profoundly influenced by the estrogen status. LMHFV significantly improved fracture healing in ovariectomized (OVX) mice being estrogen deficient, whereas bone regeneration was significantly reduced in non-OVX, estrogen-competent mice. Furthermore, estrogen receptors α (ERα) and β (ERβ) were differentially expressed in the fracture callus after whole-body vibration, depending on the estrogen status. Based on these data, we hypothesized that ERs may mediate vibration-induced effects on fracture healing. To prove this hypothesis, we investigated the effects of LMHFV on bone healing in mice lacking ERα or ERβ. To study the influence of the ER ligand estrogen, both non-OVX and OVX mice were used. All mice received a femur osteotomy stabilized by an external fixator. Half of the mice were sham-operated or subjected to OVX 4 weeks before osteotomy. Half of each group received LMHFV with 0.3 g and 45 Hz for 20 min per day, 5 days per week. After 21 days, fracture healing was evaluated by biomechanical testing, μCT analysis, histomorphometry and immunohistochemistry. Absence of ERα or ERβ did not affect fracture healing in sham-treated mice. Wildtype (WT) and ERβ-knockout mice similarly displayed impaired bone regeneration after OVX, whereas ERα-knockout mice did not. Confirming previous data, in WT mice, LMHFV negatively affected bone repair in non-OVX mice, whereas OVX-induced compromised healing was significantly improved by vibration. In contrast, vibrated ERα-knockout mice did not display significant differences in fracture healing compared to non-vibrated animals, both in non-OVX and OVX mice. Fracture healing in ERβ-knockout mice was similarly affected by LMHFV as in WT mice. These results suggest that ERα-signaling may be crucial for vibration-induced effects on fracture healing, whereas ERβ-signaling may play a minor role.
低强度高频振动（LMHFV）的机械刺激已被证明在小鼠和人类的完整骨骼中具有促合成代谢作用。然而，实验研究表明，在骨折愈合过程中，全身振动的效果受雌激素状态的深刻影响。LMHFV 显著改善了去卵巢（OVX）缺乏雌激素的小鼠的骨折愈合，而在非 OVX、雌激素功能正常的小鼠中，骨再生则显著减少。此外，全身振动后骨折痂中的雌激素受体 α（ERα）和β（ERβ）表达不同，这取决于雌激素状态。基于这些数据，我们假设 ER 可能介导振动对骨折愈合的影响。为了证明这一假设，我们研究了 LMHFV 对缺乏 ERα 或 ERβ 的小鼠骨愈合的影响。为了研究 ER 配体雌激素的影响，我们同时使用了非 OVX 和 OVX 小鼠。所有小鼠均接受股骨切开复位术，并用外固定器固定。一半的小鼠进行假手术或在切开复位前 4 周进行 OVX。每组的一半接受 LMHFV，每天 0.3g 和 45Hz，每天 20 分钟，每周 5 天。21 天后，通过生物力学测试、μCT 分析、组织形态计量学和免疫组织化学评估骨折愈合。缺乏 ERα 或 ERβ 并不影响假手术处理的小鼠的骨折愈合。野生型（WT）和 ERβ 敲除小鼠在 OVX 后同样表现出骨再生受损，而 ERα 敲除小鼠则没有。证实了先前的数据，在 WT 小鼠中，LMHFV 对非 OVX 小鼠的骨修复有负面影响，而 OVX 引起的愈合受损则显著改善。相反，振动的 ERα 敲除小鼠与非振动动物相比，在非 OVX 和 OVX 小鼠中，骨折愈合均无显著差异。在 ERβ 敲除小鼠中，LMHFV 对骨折愈合的影响与 WT 小鼠相似。这些结果表明，ERα 信号可能对振动对骨折愈合的影响至关重要，而 ERβ 信号可能作用较小。
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