Knockdown of the pericellular matrix molecule perlecan lowers in situ cell and matrix stiffness in developing cartilage.
Knockdown of the pericellular matrix molecule perlecan lowers in situ cell and matrix stiffness in developing cartilage.
复制标题
细胞周基质分子基底蛋白聚糖的敲低可降低发育中软骨的原位细胞和基质硬度。
DOI：
10.1016/j.ydbio.2016.08.029
复制
发表时间：
2016
影响因子：
2.7
通讯作者：
Calve,Sarah
中科院分区：
文献类型：
--
作者：
Xu,Xin;Li,Zhiyu;Leng,Yue;Neu,CoreyP;Calve,Sarah
细胞外基质(PCM)是细胞外基质的一种成分，在发育中和成年软骨中直接存在于单个软骨细胞周围，富含蛋白多糖。Perlecan的突变是几种发育障碍的基础，这些疾病被认为是由于PCM机械稳定性的破坏而引起的。我们通过将Perlecan被击倒的Schwartz-Jampel综合征小鼠模型与我们新的原子力显微镜技术相结合，验证了PCM组织缺陷将降低软骨细胞在发育中的软骨细胞硬度的假设，该技术可以原位测量胚胎和出生后组织中活细胞和周围基质的硬度。Perlecan基因敲除改变了基质组织，并显著降低了软骨细胞和间质基质的硬度，这是年龄和基因的函数。我们的结果表明，空间受限的基质分子的击倒可以对细胞和组织的硬度产生深远的影响，这意味着来自PCM的由外向内的机械信号在调节软骨整体发育所需的细胞内机制方面发挥了作用。
The pericellular matrix (PCM) is a component of the extracellular matrix that is found immediately surrounding individual chondrocytes in developing and adult cartilage, and is rich in the proteoglycan perlecan. Mutations in perlecan are the basis of several developmental disorders, which are thought to arise from disruptions in the mechanical stability of the PCM. We tested the hypothesis that defects in PCM organization will reduce the stiffness of chondrocytes in developing cartilage by combining a murine model of Schwartz-Jampel syndrome, in which perlecan is knocked down, with our novel atomic force microscopy technique that can measure the stiffness of living cells and surrounding matrix in embryonic and postnatal tissues in situ. Perlecan knockdown altered matrix organization and significantly decreased the stiffness of both chondrocytes and interstitial matrix as a function of age and genotype. Our results demonstrate that the knockdown of a spatially restricted matrix molecule can have a profound influence on cell and tissue stiffness, implicating a role for outside-in mechanical signals from the PCM in regulating the intracellular mechanisms required for the overall development of cartilage.