Depletion of chondrocyte primary cilia reduces the compressive modulus of articular cartilage.

Depletion of chondrocyte primary cilia reduces the compressive modulus of articular cartilage.
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DOI:
10.1016/j.jbiomech.2013.11.040
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发表时间:
2014-01-22
影响因子:
2.4
通讯作者:
Knight, Martin M.
Knight, Martin M.
中科院分区:
工程技术3区
文献类型:
--
作者:
Irianto, Jerome;Ramaswamy, Girish;Serra, Rosa;Knight, Martin M.

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初级纤毛是细长的微管结构,存在于大多数细胞类型中,每个细胞有一根纤毛。在关节软骨中,初级纤毛是软骨细胞机械转导和健康组织发育所必需的。Col2aCre原发性纤毛的丧失ift88fl/fl转基因小鼠导致骨关节炎(OA)标志物上调,骨性关节炎样软骨发育,软骨厚度增加,机械刚度降低。然而,目前还没有研究表明,初级纤毛的缺失是否会影响关节软骨基质的固有力学性能(以模量的形式)或仅影响组织的结构特性。本文描述了一种修正的分析模型,用于在以往实验压痕数据的基础上推导粘弹性模量。结果表明:Col2aCre关节软骨厚度增加;Ift88fl /fl转基因小鼠与压痕菌株瞬时模量和平衡模量的降低均大于20%相关。这表明,初级纤毛的损失导致软骨的机械性能显著降低,特别是在较深的区域和可能的底层骨。这与组织学分析一致,证实了初级纤毛在机械功能关节软骨发育中的重要性。
Primary cilia are slender, microtubule based structures found in the majority of cell types with one cilium per cell. In articular cartilage, primary cilia are required for chondrocyte mechanotransduction and the development of healthy tissue. Loss of primary cilia in Col2aCre;ift88fl/fl transgenic mice results in up-regulation of osteoarthritic (OA) markers and development of OA like cartilage with greater thickness and reduced mechanical stiffness. However no previous studies have examined whether loss of primary cilia influences the intrinsic mechanical properties of articular cartilage matrix in the form of the modulus or just the structural properties of the tissue. The present study describes a modified analytical model to derive the viscoelastic moduli based on previous experimental indentation data. Results show that the increased thickness of the articular cartilage in the Col2aCre;ift88fl/fl transgenic mice is associated with a reduction in both the instantaneous and equilibrium moduli at indentation strains of greater than 20%. This reveals that the loss of primary cilia causes a significant reduction in the mechanical properties of cartilage particularly in the deeper zones and possibly the underlying bone. This is consistent with histological analysis and confirms the importance of primary cilia in the development of a mechanically functional articular cartilage.
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