Ageing is associated with reduction of mechanically-induced activation of Smad2/3P signaling in articular cartilage

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• 作者：W. Madejp>&dagger ; p>p> ; p>p>&Dagger ; p>p> ; p>p>Wojciech.Madej@radboudumc.nl" class="auth_mail" title="E-mail the corresponding authorp> ; A. van Caamp>&Dagger ; p>p> ; p>p>Arjan.vanCaam@radboudumc.nl" class="auth_mail" title="E-mail the corresponding authorp> ; E.N. Blaney Davidsonp>&Dagger ; p>p> ; p>p>Esmeralda.BlaneyDavidson@radboudumc.nl" class="auth_mail" title="E-mail the corresponding authorp> ; G. Hanninkp>&dagger ; p>p> ; p>p>Gerjon.Hannink@radboudumc.nl" class="auth_mail" title="E-mail the corresponding authorp> ; P. Bumap>&dagger ; p>p> ; p>p>Pieter.Buma@radboudumc.nl" class="auth_mail" title="E-mail the corresponding authorp> ; P.M. van der Kraanp>&Dagger ; p>p> ; p>p>Peter.vanderKraan@radboudumc.nl" class="auth_mail" title="E-mail the corresponding authorp>
• 关键词：Cartilage ; Ageing ; TGF-beta ; Smad2/3P signaling ; Mechanosensitivity ; Signal transduction
• 刊名：Osteoarthritis and Cartilage
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：24
• 期：1
• 页码：146-157
• 全文大小：3007 K

文摘

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.p>

Design

<p id="abspara0015">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.p>

Results

<p id="abspara0020">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 (m>Col2a1m>) and fibronectin m>(Fn1)m> expression to a far lesser extent than in young cartilage. Additionally, in aged cartilage no mechanically mediated up-regulation of bone morphogenetic protein 2 (m>Bmp2m>) and connective tissue growth factor (m>Ctgfm>) was observed.p>

Conclusions

<p id="abspara0025">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).