title: ERK activation is required for hydrostatic pressure-induced tensile changes in engineered articular cartilage.
abstract: The objective of this study was to identify ERK 1/2 involvement in the changes in compressive and tensile mechanical properties associated with hydrostatic pressure treatment of self-assembled cartilage constructs. In study 1, ERK 1/2 phosphorylation was detected by immunoblot, following application of hydrostatic pressure (1 h of static 10 MPa) applied at days 10-14 of self-assembly culture. In study 2, ERK 1/2 activation was blocked during hydrostatic pressure application on days 10-14. With pharmacological inhibition of the ERK pathway by the MEK1/ERK inhibitor U0126 during hydrostatic pressure application on days 10-14, the increase in Young's modulus induced by hydrostatic pressure was blocked. Furthermore, this reduction in Young's modulus with U0126 treatment during hydrostatic pressure application corresponded to a decrease in total collagen expression. However, U0126 did not inhibit the increase in aggregate modulus or GAG induced by hydrostatic pressure. These findings demonstrate a link between hydrostatic pressure application, ERK signalling and changes in the biomechanical properties of a tissue-engineered construct.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: DuRaine
authors.forename: K A
authors.initials: KA
authors.lastname: Athanasiou
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D006874:Hydrostatic Pressure; D020935:MAP Kinase Signaling System; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D023822:Tissue Engineering
chemical_list: D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D048052:Mitogen-Activated Protein Kinase 3