Finite element modelling predicts changes in joint shape and cell behaviour due to loss of muscle strain in jaw development.
Finite element modelling predicts changes in joint shape and cell behaviour due to loss of muscle strain in jaw development.
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DOI：
10.1016/j.jbiomech.2015.07.017
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发表时间：
2015-09-18
影响因子：
2.4
通讯作者：
Hammond CL
中科院分区：
文献类型：
--
作者：
Brunt LH;Norton JL;Bright JA;Rayfield EJ;Hammond CL
异常关节形态发生与临床病症如髋关节发育不良（DDH）和骨关节炎（OA）有关。肌肉活动在关节形态发生的发育过程中是非常重要的。然而，很少有人知道这种机械刺激如何影响关节细胞的行为，以产生改变形态。使用斑马鱼，我们可以在高分辨率下对所有关节肌肉骨骼组织进行成像，我们表明通过麻醉或遗传操作去除肌肉活动会导致Meckel软骨和Palatoquadrate（下颌关节）之间的关节形状发生变化，因此关节发育不对称，导致内侧软骨元件重叠，从而抑制正常的关节功能。我们确定肌肉活动对产生正常关节至关重要的时间。使用有限元分析（FEA），模拟肌肉对骨骼元素施加的应变，我们确定最小主应变位于关节的内侧区域和张口期间的中间区域。然后，通过研究紧邻关节的细胞，我们证明了生物力学应变调节发育中关节内的细胞取向，使得当肌肉诱导的应变被去除时，关节内侧的细胞显著改变它们的取向。总之，这些数据表明，在发育过程中，需要生物力学力来建立关节的对称性。
Abnormal joint morphogenesis is linked to clinical conditions such as Developmental Dysplasia of the Hip (DDH) and to osteoarthritis (OA). Muscle activity is known to be important during the developmental process of joint morphogenesis. However, less is known about how this mechanical stimulus affects the behaviour of joint cells to generate altered morphology. Using zebrafish, in which we can image all joint musculoskeletal tissues at high resolution, we show that removal of muscle activity through anaesthetisation or genetic manipulation causes a change to the shape of the joint between the Meckel's cartilage and Palatoquadrate (the jaw joint), such that the joint develops asymmetrically leading to an overlap of the cartilage elements on the medial side which inhibits normal joint function. We identify the time during which muscle activity is critical to produce a normal joint. Using Finite Element Analysis (FEA), to model the strains exerted by muscle on the skeletal elements, we identify that minimum principal strains are located at the medial region of the joint and interzone during mouth opening. Then, by studying the cells immediately proximal to the joint, we demonstrate that biomechanical strain regulates cell orientation within the developing joint, such that when muscle-induced strain is removed, cells on the medial side of the joint notably change their orientation. Together, these data show that biomechanical forces are required to establish symmetry in the joint during development.