PDF(Pubmed)
Abstract：
Perlecan is a widely distributed, modular, and multifunctional heparan sulfate proteoglycan, which facilitates cellular communication with the extracellular environment to promote tissue development, tissue homeostasis, and optimization of biomechanical tissue functions. Perlecan-mediated osmotic mechanotransduction serves to regulate the metabolic activity of cells in tissues subjected to tension, compression, or shear. Perlecan interacts with a vast array of extracellular matrix (ECM) proteins through which it stabilizes tissues and regulates the proliferation or differentiation of resident cell populations. Here we examine the roles of the HS-proteoglycan perlecan in the normal and destabilized intervertebral disc. The intervertebral disc cell has evolved to survive in a hostile weight bearing, acidic, low oxygen tension, and low nutrition environment, and perlecan provides cytoprotection, shields disc cells from excessive compressive forces, and sequesters a range of growth factors in the disc cell environment where they aid in cellular survival, proliferation, and differentiation. The cells in mechanically destabilized connective tissues attempt to re-establish optimal tissue composition and tissue functional properties by changing the properties of their ECM, in the process of chondroid metaplasia. We explore the possibility that perlecan assists in these cell-mediated tissue remodeling responses by regulating disc cell anabolism. Perlecan\'s mechano-osmotic transductive property may be of potential therapeutic application.
摘要：
Perlecan是一种分布广泛的，模块化，和多功能硫酸乙酰肝素蛋白聚糖，促进细胞与细胞外环境的通讯，以促进组织发育，组织稳态，和生物力学组织功能的优化。Perlecan介导的渗透机械转导用于调节受张力影响的组织中细胞的代谢活性，压缩，或剪切。Perlecan与大量细胞外基质（ECM）蛋白相互作用，通过这些蛋白稳定组织并调节常驻细胞群的增殖或分化。在这里，我们研究了HS-蛋白聚糖perlecan在正常和不稳定的椎间盘中的作用。椎间盘细胞已经进化到可以在敌对的负重中生存，酸性,低氧张力,和低营养环境，Perlecan提供细胞保护，保护圆盘细胞免受过度的压缩力，并在椎间盘细胞环境中隔离一系列生长因子，它们有助于细胞存活，扩散,和差异化。机械不稳定的结缔组织中的细胞试图通过改变其ECM的特性来重新建立最佳的组织组成和组织功能特性。在软骨样化生的过程中。我们探索了perlecan通过调节椎间盘细胞合成代谢来协助这些细胞介导的组织重塑反应的可能性。Perlecan的机械渗透转导特性可能具有潜在的治疗应用。
