title: Effects of tensile strain and fluid flow on osteoarthritic human chondrocyte metabolism in vitro.
abstract: This study examined the hypothesis that tensile strain and fluid flow differentially influence osteoarthritic human chondrocyte metabolism. Primary high-density monolayer chondrocytes cultures were exposed to varying magnitudes of tensile strain and fluid-flow using a four-point bending system. Metabolic changes were quantified by real-time PCR measurement of aggrecan, IL-6, SOX-9, and type II collagen gene expression, and by determination of nitric oxide levels in the culture medium. A linear regression model was used to investigate the roles of strain, fluid flow, and their interaction on metabolic activity. Aggrecan, type II collagen, and SOX9 mRNA expression were negatively correlated to increases in applied strain and fluid flow. An effect of the strain on the induction of nitric oxide release and IL-6 gene expression varied by level of fluid flow (and visa versa). This interaction between strain and fluid flow was negative for nitric oxide and positive for IL-6. These results confirm that articular chondrocyte metabolism is responsive to tensile strain and fluid flow under in vitro loading conditions. Although the articular chondrocytes reacted to the mechanically applied stress, it was notable that there was a differential effect of tensile strain and fluid flow on anabolic and catabolic markers.
authors.affiliation: Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, 300 Pasteur Drive, R105, Stanford, California 94305, USA.
authors.forename: Taro
authors.initials: T
authors.lastname: Mawatari
authors.forename: Derek P
authors.initials: DP
authors.lastname: Lindsey
authors.forename: Alex H S
authors.initials: AH
authors.lastname: Harris
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: William J
authors.initials: WJ
authors.lastname: Maloney
authors.forename: Robert L
authors.initials: RL
authors.lastname: Smith
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D024043:Collagen Type II / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000235:genetics; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology*; D016474:Weight-Bearing / Q000502:physiology
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D024043:Collagen Type II; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D009569:Nitric Oxide