Differential effects of altered patterns of movement and strain on joint cell behaviour and skeletal morphogenesis.
Differential effects of altered patterns of movement and strain on joint cell behaviour and skeletal morphogenesis.
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DOI：
10.1016/j.joca.2016.06.015
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发表时间：
2016-11
影响因子：
7
通讯作者：
Hammond, C. L.
中科院分区：
文献类型：
--
作者：
Brunt, L. H.;Skinner, R. E. H.;Roddy, K. A.;Araujo, N. M.;Rayfield, E. J.;Hammond, C. L.
越来越多的证据表明，关节形状是骨关节炎（OA）风险的一个有效预测因子，但支撑关节形态发生的细胞事件仍不清楚。我们试图开发一种遗传学上易于处理的动物模型来研究控制关节形态发生的事件。斑马鱼幼体经历了弛缓性麻痹、僵硬性麻痹或过度活跃的时期。免疫组织化学和转基因报告用于监测肌肉和软骨的变化。有限元模型的生成，以研究僵硬瘫痪的力学条件。主成分分析用于测试骨骼形态的变化，形状、方向和大小的度量用于描述细胞行为。我们表明，弛缓性和僵硬性瘫痪和过度活动影响软骨元素和关节形状。我们描述了肌肉收缩时表现出高主应变的区域中松弛性瘫痪和僵硬性瘫痪之间的差异。我们确定，改变形状和高应变发生在细胞分化的区域，我们显示统计学上显着的变化，细胞成熟度发生在这些地区的瘫痪和高机动性斑马鱼。虽然弛缓性和僵硬性麻痹以及过度活动影响骨骼形态发生，但它们的影响方式略有不同。我们发现，一些软骨区域是不受影响的条件下，如僵硬的瘫痪，其中施加静力，而关节形态发生的松弛和僵硬的瘫痪扰动，这表明关节需要动态运动，准确的形态发生。更好地理解生物力学如何影响骨骼细胞的行为将提高我们对胎儿力学如何塑造发育中的关节的理解。
There is increasing evidence that joint shape is a potent predictor of osteoarthritis (OA) risk; yet the cellular events underpinning joint morphogenesis remain unclear. We sought to develop a genetically tractable animal model to study the events controlling joint morphogenesis. Zebrafish larvae were subjected to periods of flaccid paralysis, rigid paralysis or hyperactivity. Immunohistochemistry and transgenic reporters were used to monitor changes to muscle and cartilage. Finite Element Models were generated to investigate the mechanical conditions of rigid paralysis. Principal component analysis was used to test variations in skeletal morphology and metrics for shape, orientation and size were applied to describe cell behaviour. We show that flaccid and rigid paralysis and hypermobility affect cartilage element and joint shape. We describe differences between flaccid and rigid paralysis in regions showing high principal strain upon muscle contraction. We identify that altered shape and high strain occur in regions of cell differentiation and we show statistically significant changes to cell maturity occur in these regions in paralysed and hypermobile zebrafish. While flaccid and rigid paralysis and hypermobility affect skeletal morphogenesis they do so in subtly different ways. We show that some cartilage regions are unaffected in conditions such as rigid paralysis where static force is applied, whereas joint morphogenesis is perturbed by both flaccid and rigid paralysis; suggesting that joints require dynamic movement for accurate morphogenesis. A better understanding of how biomechanics impacts skeletal cell behaviour will improve our understanding of how foetal mechanics shape the developing joint.
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影响因子：
2.4
作者：
Brunt LH;Norton JL;Bright JA;Rayfield EJ;Hammond CL
通讯作者：
Hammond CL
影响因子：
--
作者：
Diogo R;Hinits Y;Hughes SM
通讯作者：
Hughes SM
影响因子：
2.4
作者：
Pitsillides, AA
通讯作者：
Pitsillides, AA
影响因子：
2.1
作者：
Pacifici, Maurizio;Koyama, Eiki;Iwamoto, Masahiro
通讯作者：
Iwamoto, Masahiro
影响因子：
6.9
作者：
Decker, Rebekah S.;Koyama, Eiki;Pacifici, Maurizio
通讯作者：
Pacifici, Maurizio