title: Integrin-mediated mechanotransduction processes in TGFbeta-stimulated monolayer-expanded chondrocytes.
abstract: Previous studies have demonstrated that passage in monolayer detrimentally affects the response of articular chondrocytes to the application of dynamic compression. Transforming growth factor beta (TGFbeta) is known to regulate metabolic processes in articular cartilage and can enhance the re-expression of a chondrocytic phenotype following monolayer expansion. The current study tests the hypothesis that TGFbeta also modulates the response of monolayer-expanded human chondrocytes to the application of dynamic compression, via an integrin-mediated mechanotransduction process. The data presented demonstrate that TGFbeta3 enhanced 35SO4 and [3H]thymidine incorporation and inhibited nitrite release after 48 h of culture when compared to unsupplemented constructs. Dynamic compression also enhanced 35SO4 and [3H]thymidine incorporation and inhibited nitrite release in the presence of TGFbeta3. By contrast, dynamic compression did not alter these parameters in the absence of the growth factor. The addition of the peptide, GRGDSP, which acts as a competitive ligand for the alpha5beta1 integrin, reversed the compression-induced stimulation of 35SO4 incorporation, [3H]thymidine incorporation, and suppression of nitrite release. No effect was observed when the control peptide, GRADSP, was used. The current data clearly demonstrate that the dynamic compression-induced changes observed in cell metabolism for human monolayer-expanded chondrocytes were dependent on the presence of TGFbeta3 and are integrin-mediated.
authors.affiliation: Medical Engineering Division and IRC in Biomedical Materials, Department of Engineering, Queen Mary, University of London, Mile End Road, London E1 4NS, UK. T.T.Chowdhury@qmul.ac.uk
authors.forename: T T
authors.initials: TT
authors.lastname: Chowdhury
authors.forename: D M
authors.initials: DM
authors.lastname: Salter
authors.forename: D L
authors.initials: DL
authors.lastname: Bader
authors.forename: D A
authors.initials: DA
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D002356:Cartilage / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009573:Nitrites / Q000378:metabolism; D013314:Stress, Mechanical; D013462:Sulfur Radioisotopes; D013463:Sulfuric Acid Esters / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014316:Tritium
chemical_list: D003470:Culture Media; D016023:Integrins; D009573:Nitrites; D013462:Sulfur Radioisotopes; D013463:Sulfuric Acid Esters; D016212:Transforming Growth Factor beta; D014316:Tritium; D013936:Thymidine