Ageing is associated with reduction of mechanically-induced activation of Smad2/3P signaling in articular cartilage
Ageing is associated with reduction of mechanically-induced activation of Smad2/3P signaling in articular cartilage
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DOI：
10.1016/j.joca.2015.07.018
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发表时间：
2016-01-01
影响因子：
7
通讯作者：
van der Kraan, P. M.
中科院分区：
文献类型：
--
作者：
Madej, W.;van Caam, A.;van der Kraan, P. M.
目的：机械信号控制关节软骨的关键细胞过程。以前，我们已经表明，机械压缩是一个重要的ALK 5/Smad 2/3 P激活软骨外植体。然而，已知软骨中与年龄相关的变化会影响组织机械敏感性以及ALK 5/Smad 2/3 P信号传导。我们已经调查了是否老化的软骨是与一个改变的响应机械compression.Design：两个不同年龄组（年轻-6-36个月大，年龄-6 - 13岁）的关节软骨外植体进行动态机械压缩与3 MPa（生理）或12 MPa（过度）负荷。随后，通过QPCR测量年轻和老年软骨中的必需软骨细胞外基质（ECM）组分和组织生长因子基因表达。此外，分析和比较年轻和老化软骨响应于压缩激活Smad 2/3 P信号传导的能力。这是通过免疫组织化学（IH）Smad 2 P检测和Smad 3-响应基因表达analysis.Results：老年软骨表现出高度降低的能力，机械介导的激活Smad 2/3 P信号相比，年轻的软骨。压缩老年软骨，诱导胶原蛋白II型（Col 2a 1）和纤连蛋白（Fn 1）的表达，远低于年轻的软骨。此外，在老年软骨没有机械介导的上调骨形态发生蛋白2（BMP 2）和结缔组织生长因子（Ctgf）observed.Conclusions：我们确定了与年龄相关的变化，关节软骨的机械刺激的细胞反应。我们认为，这些变化可能与年龄相关的软骨功能改变有关，并可能成为骨关节炎（OA）等年龄相关软骨疾病发展的基础机制。(C)2015国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Mechanical signals control key cellular processes in articular cartilage. Previously we have shown that mechanical compression is an important ALK5/Smad2/3P activator in cartilage explants. However, age-related changes in the cartilage are known to affect tissue mechanosensitivity and also ALK5/Smad2/3P signaling. We have investigated whether ageing of cartilage is associated with an altered response to mechanical compression.Design: Articular cartilage explants of two different age groups (young-6-36 months old, aged-6 - 13 years old) were subjected to dynamic mechanical compression with 3 MPa (physiological) or 12 MPa (excessive) load. Subsequently, essential cartilage extracellular matrix (ECM) components and tissue growth factors gene expression was measured in young and aged cartilage by QPCR. Furthermore, the ability of young and aged cartilage, to activate the Smad2/3P signaling in response to compression was analyzed and compared. This was done by immunohistochemical (IH) Smad2P detection and Smad3-responsive gene expression analysis.Results: Aged cartilage showed a highly reduced capacity for mechanically-mediated activation of Smad2/3P signaling when compared to young cartilage. Compression of aged cartilage, induced collagen type II (Col2a1) and fibronectin (Fn1) expression to a far lesser extent than in young cartilage. Additionally, in aged cartilage no mechanically mediated up-regulation of bone morphogenetic protein 2 (Bmp2) and connective tissue growth factor (Ctgf) was observed.Conclusions: We identified age-related changes in cellular responses to mechanical stimulation of articular cartilage. We propose that these changes might be associated with age-related alterations in cartilage functioning and can underlie mechanisms for development of age-related cartilage diseases like osteoarthritis (OA). (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.