Effects of the local mechanical environment on vertebrate tissue differentiation during repair: does repair recapitulate development?
Effects of the local mechanical environment on vertebrate tissue differentiation during repair: does repair recapitulate development?
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DOI：
10.1242/jeb.00453
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发表时间：
2003-07-01
影响因子：
2.8
通讯作者：
Einhorn, TA
中科院分区：
文献类型：
--
作者：
Cullinane, DM;Salisbury, KT;Einhorn, TA
在脊椎动物骨骼发育和修复过程中，局部机械环境是决定细胞和组织分化的关键因素。与Wolff定律所描述的骨骼对机械负荷的基本反应不同，局部机械环境与组织分化之间的机械生物学关系影响着从组织类型和分子结构到复杂关节的形成等方方面面。本研究验证了一个假设，即精确控制机械载荷可以调节成人骨骼中的基因表达、组织分化和组织结构，并且精确操纵缺陷的局部机械环境可以启动关节组织发育的有限再现。我们利用已发表的组织分化的机械生物学命运图来解释的有限元模型（fem）来生成组织类型预测。实验包括一个定制设计的外固定架，能够引入每日弯曲，剪切或弯曲和剪切载荷组合方案，以在愈合的股骨缺损中诱导精确控制的机械条件。利用组织形态计量学和分子标记学对组织类型和比例进行表征。使用偏振光和傅里叶变换定量组织分子结构，而免疫染色和原位杂交用于表征基因表达。有限元模型预测了软骨在缺损内的分化，并且在弯曲组中，大量的纤维组织将沿着极端偏移的外围发育。三种实验诱导的加载方案在所有实验缺陷上产生连续的软骨带，抑制骨愈合。实验组软骨与骨之比的组织形态学分析与膝关节没有显著差异，傅里叶变换分析发现，所有实验软骨的浅层、中层和深层胶原纤维的角度专门化存在显著差异(P
The local mechanical environment is a crucial factor in determining cell and tissue differentiation during vertebrate skeletal development and repair. Unlike the basic response of bone to mechanical load, as described in Wolff's law, the mechanobiological relationship between the local mechanical environment and tissue differentiation influences everything from tissue type and molecular architecture to the formation of complex joints. This study tests the hypothesis that precisely controlled mechanical loading can regulate gene expression, tissue differentiation and tissue architecture in the adult skeleton and that precise manipulation of the defect's local mechanical environment can initiate a limited recapitulation of joint tissue development. We generated tissue type predictions using finite element models (FEMs) interpreted by published mechanobiological fate maps of tissue differentiation. The experiment included a custom-designed external fixator capable of introducing daily bending, shear or a combination of bending and shear load regimens to induce precisely controlled mechanical conditions within healing femoral defects. Tissue types and ratios were characterized using histomorphometrics and molecular markers. Tissue molecular architecture was quantified using polarized light and Fourier transforms, while immunological staining and in situ hybridization were used to characterize gene expression. The finite element models predicted the differentiation of cartilage within the defects and that substantial fibrous tissues would develop along the extreme excursion peripheries in the bending group. The three experimentally induced loading regimens produced contiguous cartilage bands across all experimental defects, inhibiting bony healing. Histomorphometric analysis of the ratios of cartilage to bone in the experimental groups were not significantly different from those for the knee joint, and Fourier transform analysis determined significantly different collagen fibril angle specializations within superficial, intermediate and deep layers of all experimental cartilages (P