Local mechanical stimuli correlate with tissue growth in axolotl salamander joint morphogenesis.
Local mechanical stimuli correlate with tissue growth in axolotl salamander joint morphogenesis.
复制标题
局部机械刺激与蝾螈关节形态发生有关。
DOI：
10.1098/rspb.2022.0621
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发表时间：
2022-05-25
影响因子：
4.7
通讯作者：
Shefelbine, Sandra J.
中科院分区：
文献类型：
--
作者：
Comellas, Ester;Farkas, Johanna E.;Kleinberg, Giona;Lloyd, Katlyn;Mueller, Thomas;Duerr, Timothy J.;Munoz, Jose J.;Monaghan, James R.;Shefelbine, Sandra J.
关键词：
运动诱导的力对于关节的正确形成至关重要，但目前尚不清楚细胞如何感知并响应这些力学信号。为研究机械刺激在关节塑形中的作用，我们将对墨西哥钝口螈（Ambystoma mexicanum）前肢再生的实验与骨骼原基生长的多孔弹性模型相结合。实验动物的前肢要么正常再生（对照组），要么在关节形态发生过程中注射瞬时受体电位香草酸亚型4（TRPV4）激动剂。我们通过对再生肢体进行整装光片荧光成像，量化了再生肱骨的生长情况和形状。结果显示，不同组之间在形态和细胞增殖方面存在显著差异，这表明TRPV4脱敏对关节形状有影响。为了将TRPV4脱敏与机械敏感性受损联系起来，我们构建了再生肱骨的有限元模型。局部组织生长是由与软骨细胞密度成正比的生物学贡献（该贡献恒定）和与流体压力成正比的力学贡献之和构成。生长的计算预测结果与关节形状的实验结果相符，这表明周期性机械刺激产生的间质压力促进了局部组织生长。由实验结果提供信息的预测性计算模型使我们能够探索组织生长中潜在的物理机制，从而增进我们对关节形态发生的力学生物学的理解。
Movement-induced forces are critical to correct joint formation, but it is unclear how cells sense and respond to these mechanical cues. To study the role of mechanical stimuli in the shaping of the joint, we combined experiments on regenerating axolotl (Ambystoma mexicanum) forelimbs with a poroelastic model of bone rudiment growth. Animals either regrew forelimbs normally (control) or were injected with a transient receptor potential vanilloid 4 (TRPV4) agonist during joint morphogenesis. We quantified growth and shape in regrown humeri from whole-mount light sheet fluorescence images of the regenerated limbs. Results revealed significant differences in morphology and cell proliferation between groups, indicating that TRPV4 desensitization has an effect on joint shape. To link TRPV4 desensitization with impaired mechanosensitivity, we developed a finite element model of a regenerating humerus. Local tissue growth was the sum of a biological contribution proportional to chondrocyte density, which was constant, and a mechanical contribution proportional to fluid pressure. Computational predictions of growth agreed with experimental outcomes of joint shape, suggesting that interstitial pressure driven from cyclic mechanical stimuli promotes local tissue growth. Predictive computational models informed by experimental findings allow us to explore potential physical mechanisms involved in tissue growth to advance our understanding of the mechanobiology of joint morphogenesis.
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影响因子：
--
作者：
Guimond JC;Lévesque M;Michaud PL;Berdugo J;Finnson K;Philip A;Roy S
通讯作者：
Roy S
影响因子：
3.7
作者：
Jin M;Wu Z;Chen L;Jaimes J;Collins D;Walters ET;O'Neil RG
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O'Neil RG
影响因子：
7
作者：
Cosden-Decker, R. S.;Bickett, M. M.;Lattermann, C.;MacLeod, J. N.
通讯作者：
MacLeod, J. N.
影响因子：
7
作者：
Brunt, L. H.;Skinner, R. E. H.;Roddy, K. A.;Araujo, N. M.;Rayfield, E. J.;Hammond, C. L.
通讯作者：
Hammond, C. L.
影响因子：
7
作者：
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通讯作者：
Knight MM