Early effects of embryonic movement: 'a shot out of the dark'
Early effects of embryonic movement: 'a shot out of the dark'
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DOI：
10.1111/j.1469-7580.2006.00556.x
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发表时间：
2006-04-01
影响因子：
2.4
通讯作者：
Pitsillides, AA
中科院分区：
文献类型：
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作者：
Pitsillides, AA
长期以来人们就认识到，对卵内胚胎鸡进行研究具有多种优势，包括有可能在不受母体影响的情况下控制胚胎的环境及其运动。这使得早期的研究人员能够确定运动是运动器官发育的关键因素。随着对最早可检测到的运动的关注日益增加，我们通过开发新的模型和方案来利用这一系统，以研究肌肉骨骼发育过程中特定运动时期的影响。利用具有已知神经肌肉作用的药物来诱发过度活动（4 - 氨基吡啶，AP）以及强直性（溴化十烃季铵，DMB）或弛缓性（溴化潘库铵，PB）麻痹，我们研究了运动在关节、骨软骨和肌肉发育中的作用。我们最初针对关节的研究表明，AP诱导的过度活动对关节腔形成的时间或范围几乎没有（如果有的话）影响，这表明内源性活动水平提供了足够的刺激，额外的活动并无效果。相比之下，在关节腔形成之前施加强直性或弛缓性麻痹会完全阻断这一过程，并且随着时间的推移，会导致软骨成分融合，并在通常会形成关节的部位形成连续的单一软骨棒。然而，当在明显的关节腔形成之后开始治疗时，这些不同形式的麻痹效果有所不同；强直性麻痹（而非弛缓性麻痹）部分保留了已形成关节腔之前的关节结构。这一观察结果表明，源自“痉挛性”强直的“静态”负荷能够起到保护关节腔的作用。这些研究的另一个方面是观察到DMB诱导的强直性麻痹会产生一种均匀且特定的肢体畸形模式，而PB则产生了各种各样的固定位置畸形。两者也都减少了肢体生长，不同的发育时期会优先改变特定的骨软骨成分。在不同发育阶段施加3天的弛缓性固定所引起的软骨和骨生长变化，支持了早期软骨形成减少以及运动对骨生成的影响相对延迟的观点，这表明在发育中的骨骼对运动影响具有接受性的关键时期。固定对肢体的近 - 远端轴也有不同的影响。最后，我们的初步结果支持胚胎过度活动影响出生后肌肉生长潜力的可能性。
It has long been appreciated that studying the embryonic chick in ovo provides a variety of advantages, including the potential to control the embryo's environment and its movement independently of maternal influences. This allowed early workers to identify movement as a pivotal factor in the development of the locomotor apparatus. With an increasing focus on the earliest detectable movements, we have exploited this system by developing novel models and schemes to examine the influence of defined periods of movement during musculoskeletal development. Utilizing drugs with known neuromuscular actions to provoke hyperactivity (4-aminopyridine, AP) and either rigid (decamethonium bromide, DMB) or flaccid (pancuronium bromide, PB) paralysis, we have examined the role of movement in joint, osteochondral and muscle development. Our initial studies focusing on the joint showed that AP-induced hyperactivity had little, if any, effect on the timing or scope of joint cavity elaboration, suggesting that endogenous activity levels provide sufficient stimulus, and additional mobilization is without effect. By contrast, imposition of either rigid or flaccid paralysis prior to cavity formation completely blocked this process and, with time, produced fusion of cartilaginous elements and formation of continuous single cartilaginous rods across locations where joints would ordinarily form. The effect of these distinct forms of paralysis differed, however, when treatment was initiated after formation of an overt cavity; rigid, but not flaccid, paralysis partly conserved precavitated joints. This observation suggests that 'static' loading derived from 'spastic' rigidity can act to preserve joint cavities. Another facet of these studies was the observation that DMB-induced rigid paralysis produces a uniform and specific pattern of limb deformity whereas PB generated a diverse range of fixed positional deformities. Both also reduced limb growth, with different developmental periods preferentially modifying specific osteochondral components. Changes in cartilage and bone growth induced by 3-day periods of flaccid immobilization, imposed at distinct developmental phases, provides support for a diminution in cartilage elaboration at an early phase and for a relatively delayed influence of movement on osteogenesis, invoking critical periods during which the developing skeleton becomes receptive to the impact of movement. Immobilization also exerts differential impact along the proximo-distal axis of the limb. Finally, our preliminary results support the possibility that embryonic hyperactivity influences the potential for postnatal muscle growth.