Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice

Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice
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DOI:
10.1002/jor.23178
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发表时间:
2016-10-01
影响因子:
2.8
通讯作者:
Christiansen, Blaine A.
Christiansen, Blaine A.
中科院分区:
医学3区
文献类型:
--
作者:
Anderson, Matthew J.;Diko, Sindi;Christiansen, Blaine A.

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骨关节炎的发展通常涉及骺骨小梁的变性。在先前的研究中,我们观察到小鼠非侵入性膝关节损伤后1周内股骨远端骺骨小梁(BV/TV)损失30-44%。机械卸载(废用)可能导致这种骨丢失;然而,目前尚不清楚受伤肢体在受伤后的卸载程度,以及废用是否可以完全解释所观察到的骨丢失程度。在这项研究中,我们研究了机械卸载对小鼠(雌性C57 BL/6 N)非侵入性膝关节损伤后观察到的骨小梁变化的贡献。我们研究了在跑步机行走过程中步态的变化,以及在受伤后4、14、28和42天使用开放视野分析的自愿活动水平的变化。我们还使用CT对骨骺骨小梁进行定量,并对下肢肌肉进行称重,以量化地面对照和后肢未负荷(HLU)小鼠膝关节损伤后的萎缩。步态分析显示,受伤肢体的步幅模式略有改变,站立阶段减少,摆动阶段增加。然而,旷场分析显示,在任何时间点,受伤和假手术小鼠之间的自主运动没有差异。膝关节损伤和HLU均导致相当程度的骨小梁丢失;然而,HLU导致的肌肉丢失比膝关节损伤多得多,表明损伤后导致骨丢失的另一种机制。总之,这些数据表明,机械卸载可能有助于非侵入性膝关节损伤后的骨小梁丢失,但这种骨丢失的程度不能完全解释废用。(c)2016骨科研究学会。出版社:Wiley Periodicals,Inc. J Orthop Res 34:1680-1687,2016.
Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30-44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within 1 week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss; however, it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using CT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss; however, HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1680-1687, 2016.