Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone.

Reduced gravitational loading does not account for the skeletal effect of botulinum toxin-induced muscle inhibition suggesting a direct effect of muscle on bone.
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重力负荷的减少并不能解释肉毒杆菌毒素诱导的肌肉抑制对骨骼的影响,表明肌肉对骨骼的直接影响。

DOI:
10.1016/j.bone.2013.01.043
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发表时间:
2013
期刊:
影响因子:
4.1
通讯作者:
Fuchs,RobynK
Fuchs,RobynK
中科院分区:
医学2区
文献类型:
--
作者:
Warden,StuartJ;Galley,MatthewR;Richard,JeffreyS;George,LydiaA;Dirks,RachelC;Guildenbecher,ElizabethA;Judd,AshleyM;Robling,AlexanderG;Fuchs,RobynK

文献摘要

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在啮齿类动物后肢肌内注射肉毒杆菌毒素(botox)已发展成为探索肌肉-骨相互作用的有用模型。肉毒杆菌诱导的肌肉抑制迅速引起肌肉萎缩和随后的骨质流失,后者被认为是骨骼肌肉负荷减少的结果。然而,肉毒杆菌诱导的肌肉抑制也减少了重力负荷(如步态时地面反作用力的减少),这可能解释了其对骨骼的负面影响。本研究的目的是研究肉毒杆菌毒素诱导的肌肉抑制对笼子对照和尾巴悬吊小鼠的骨骼影响,尾巴悬吊用于控制与肉毒杆菌毒素相关的重力负荷减少。雌性C57BL/6J小鼠单侧注射肉毒杆菌素,对侧注射载药,然后悬尾或正常笼活动6周。肉毒杆菌诱导的肌肉抑制联合悬尾对骨骼的有害影响最大,导致胫骨中轴骨量、皮质面积和皮质厚度的增加最小,胫骨中轴髓面积的增加最大,胫骨近端小梁骨体积分数最低。这些数据表明肉毒杆菌诱导的肌肉抑制对骨骼的影响超过了它在改变重力负荷方面的任何影响,这表明肌肉对骨骼有直接影响。这种效应可能与针对肌肉骨骼健康的策略的发展有关。
Intramuscular injection of botulinum toxin (botox) into rodent hindlimbs has developed as a useful model for exploring muscle–bone interactions. Botox-induced muscle inhibition rapidly induces muscle atrophy and subsequent bone loss, with the latter hypothesized to result from reduced muscular loading of the skeleton. However, botox-induced muscle inhibition also reduces gravitational loading (as evident by reduced ground reaction forces during gait) which may account for its negative skeletal effects. The aim of this study was to investigate the skeletal effect of botox-induced muscle inhibition in cage control and tail suspended mice, with tail suspension being used to control for the reduced gravitational loading associated with botox. Female C57BL/6J mice were injected unilaterally with botox and contralaterally with vehicle, and subsequently exposed to tail suspension or normal cage activities for 6weeks. Botox-induced muscle inhibition combined with tail suspension had the largest detrimental effect on the skeleton, causing the least gains in midshaft tibial bone mass, cortical area and cortical thickness, greatest gains in midshaft tibial medullary area, and lowest proximal tibial trabecular bone volume fraction. These data indicate botox-induced muscle inhibition has skeletal effects over and above any effect it has in altering gravitational loading, suggesting that muscle has a direct effect on bone. This effect may be relevant in the development of strategies targeting musculoskeletal health.