Extracellular matrix ligand and stiffness modulate immature nucleus pulposus cell-cell interactions.
Extracellular matrix ligand and stiffness modulate immature nucleus pulposus cell-cell interactions.
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DOI：
10.1371/journal.pone.0027170
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Setton LA
中科院分区：
文献类型：
--
作者：
Gilchrist CL;Darling EM;Chen J;Setton LA
椎间盘的髓核 (NP) 的功能是为脊柱提供压缩负载支撑，并且包含在该组织的生成和维护中发挥关键作用的细胞。 NP细胞群在成熟和衰老过程中经历显着的形态和表型变化，从排列成细胞簇的大的、空泡的未成熟细胞转变为较小的、孤立的软骨细胞样细胞的稀疏群。这些形态和组织变化似乎与椎间盘内退行性变化的最初迹象相关。未成熟的 NP 的细胞外基质是一种柔软的凝胶状材料，含有多种层粘连蛋白亚型，这些特征是 NP 相对于椎间盘其他区域所独有的，并且会随着老化和退化而变化。基于这些知识，我们假设柔软、富含层粘连蛋白的细胞外基质环境将促进 NP 细胞-细胞相互作用和与未成熟 NP 组织中发现的类似的表型。 NP 细胞从猪椎间盘中分离出来，并在不同机械刚度的基质环境中培养，并用各种基质配体进行功能化；使用细胞组织和表型的定量测量来评估细胞对培养时期的反应。结果表明，柔软（<720 Pa）、含层粘连蛋白的细胞外基质基质可促进 NP 细胞形态、细胞间相互作用和体外蛋白聚糖的产生，并且这种行为取决于细胞外基质配体和基质机械性能。这些发现表明，NP 细胞组织和表型可能对其周围的细胞外基质环境高度敏感。
The nucleus pulposus (NP) of the intervertebral disc functions to provide compressive load support in the spine, and contains cells that play a critical role in the generation and maintenance of this tissue. The NP cell population undergoes significant morphological and phenotypic changes during maturation and aging, transitioning from large, vacuolated immature cells arranged in cell clusters to a sparse population of smaller, isolated chondrocyte-like cells. These morphological and organizational changes appear to correlate with the first signs of degenerative changes within the intervertebral disc. The extracellular matrix of the immature NP is a soft, gelatinous material containing multiple laminin isoforms, features that are unique to the NP relative to other regions of the disc and that change with aging and degeneration. Based on this knowledge, we hypothesized that a soft, laminin-rich extracellular matrix environment would promote NP cell-cell interactions and phenotypes similar to those found in immature NP tissues. NP cells were isolated from porcine intervertebral discs and cultured in matrix environments of varying mechanical stiffness that were functionalized with various matrix ligands; cellular responses to periods of culture were assessed using quantitative measures of cell organization and phenotype. Results show that soft (<720 Pa), laminin-containing extracellular matrix substrates promote NP cell morphologies, cell-cell interactions, and proteoglycan production in vitro, and that this behavior is dependent upon both extracellular matrix ligand and substrate mechanical properties. These findings indicate that NP cell organization and phenotype may be highly sensitive to their surrounding extracellular matrix environment.
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DOI：
10.1016/s0006-291x(02)00314-5
发表时间：
2002-05-10
影响因子：
3.1
作者：
Chen, J;Baer, AE;Setton, LA
通讯作者：
Setton, LA
影响因子：
2.5
作者：
Choi, Kyung-Suk;Cohn, Martin J.;Harfe, Brian D.
通讯作者：
Harfe, Brian D.
影响因子：
3.4
作者：
Engler, A;Bacakova, L;Discher, D
通讯作者：
Discher, D
影响因子：
3
作者：
BUCKWALTER, JA
通讯作者：
BUCKWALTER, JA
影响因子：
2.4
作者：
Darling, Eric M.;Topel, Matthew;Guilak, Farshid
通讯作者：
Guilak, Farshid