Hyaluronan and CD44 - Modulators of chondrocyte metabolism
Hyaluronan and CD44 - Modulators of chondrocyte metabolism
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DOI：
10.1097/01.blo.0000143804.26638.82
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发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Knudson, W
中科院分区：
文献类型：
--
作者：
Knudson, CB;Knudson, W
细胞-基质相互作用的稳定性促进了组织的动态平衡，而基质受体提供了基质的组装和保持以及与响应细胞外基质内变化而激活的信号转导通路的联系。因此，细胞-基质相互作用的改变可能会影响细胞对细胞因子的反应和细胞的存活，并可能促进组织重塑。基质成分将可溶性的形态原隔离或呈递给它们的信号受体。另一层复杂性将是建立新的或解偶联的细胞-基质相互作用，导致细胞对形态因子的反应改变。透明质酸受体CD44是透明质酸-蛋白多糖聚集在软骨细胞表面的关键环节。随着我们继续定义功能性软骨细胞CD44，未来的研究将需要包括对CD44异构体表达、磷酸化、细胞骨架相互作用、占位和周转的分析。破坏软骨细胞CD44：透明质酸的相互作用将引发一系列事件，导致分解代谢和合成代谢基因产物的激活。在自由基过程中产生的透明质酸片段有可能在CD44依赖的机制中增加一氧化氮的产生。数据还支持一种新兴的范式，即CD44介导的信号既影响软骨细胞的生存途径，也影响细胞的凋亡途径。
Stability of cell-matrix interactions promotes tissue homeostasis, and matrix receptors provide for the assembly and retention of matrix as well as the linkage to the signal transduction pathways activated in response to changes within the extracellular matrix. Therefore, changes in cell-matrix interactions may influence cell responses to cytokines and cell survival and may facilitate tissue remodeling. Matrix components sequester or present soluble morphogens to their signaling receptors. Another layer of complexity would be the establishment of new or uncoupling of cell-matrix interactions, leading to altered cellular response to morphogens. The hyaluronan receptor CD44 serves as the critical link for the retention of hyaluronan-proteoglycan aggregates to the chondrocyte cell surface. As we continue to define functional chondrocyte CD44, future studies will need to include analysis of the variant CD44 isoform expression, phosphorylation, cytoskeletal interactions, occupancy, and turnover. Disruption of chondrocyte CD44:hyaluronan interaction will induce a cascade of events resulting in the activation of both catabolic as well as anabolic gene products. Fragments of hyaluronan produced in free radical processes have the potential to augment the production of nitric oxide in a CD44-dependent mechanism. Data also support an emerging paradigm that CD44-mediated signaling affects both chondrocyte survival pathways as well as apoptotic pathways.