Abstract
Articular cartilage is physiologically exposed to repeated loads. The mechanical properties of cartilage are due to its extracellular matrix, and homeostasis is maintained by the sole cell type found in cartilage, the chondrocyte. Although mechanical forces clearly control the functions of articular chondrocytes, the biochemical pathways that mediate cellular responses to mechanical stress have not been fully characterised. The aim of our study was to examine early molecular events triggered by dynamic compression in chondrocytes. We used an experimental system consisting of primary mouse chondrocytes embedded within an agarose hydrogel; embedded cells were pre-cultured for one week and subjected to short-term compression experiments. Using Western blots, we demonstrated that chondrocytes maintain a differentiated phenotype in this model system and reproduce typical chondrocyte-cartilage matrix interactions. We investigated the impact of dynamic compression on the phosphorylation state of signalling molecules and genome-wide gene expression. After 15 min of dynamic compression, we observed transient activation of ERK1/2 and p38 (members of the mitogen-activated protein kinase (MAPK) pathways) and Smad2/3 (members of the canonical transforming growth factor (TGF)-β pathways). A microarray analysis performed on chondrocytes compressed for 30 min revealed that only 20 transcripts were modulated more than 2-fold. A less conservative list of 325 modulated genes included genes related to the MAPK and TGF-β pathways and/or known to be mechanosensitive in other biological contexts. Of these candidate mechanosensitive genes, 85% were down-regulated. Down-regulation may therefore represent a general control mechanism for a rapid response to dynamic compression. Furthermore, modulation of transcripts corresponding to different aspects of cellular physiology was observed, such as non-coding RNAs or primary cilium. This study provides new insight into how chondrocytes respond to mechanical forces.
Highlights
Articular cartilage is a highly specialised connective tissue in joints
The results presented here indicate that the mitogen-activated protein kinase (MAPK) and the transforming growth factor (TGF)- b pathways are involved in the early response of chondrocytes to dynamic compression
Mouse chondrocytes were embedded in agarose just after their isolation from cartilage and these chondrocyte-agarose constructs were cultured for 6 days to allow extracellular matrix deposition
Summary
Articular cartilage is a highly specialised connective tissue in joints. Its main function is to provide a smooth, lubricated surface for articulation and to take up and distribute high loads. The fibrillar collagen network, mainly composed of type II collagen, provides the tissue with its tensile resistance. As the only cell type in articular cartilage, chondrocytes are entirely responsible for maintaining the metabolic balance of matrix proteins. It has been shown that mechanical forces affect chondrocyte metabolic activity (for a review, see [1]). Ex vivo and in vitro models of chondrocyte mechanobiology have generally shown that static compression inhibits the expression of cartilage matrix proteins whereas dynamic compression regimens enhance them [2,3,4,5,6,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
