title: Signal transduction pathways and apoptosis in bacteria infected chondrocytes.
abstract: The mechanism underlying chronic destructive arthropathy after pyogenic arthritis is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus infected human articular chondrocytes and investigated the signal transduction pathways activated by bacterial infection. Chondrocytes cultured in monolayer were challenged with bacteria for 6 h and were analyzed after incubation for 2, 18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of apoptosis after infection and the following incubation period. Although treatment with extensive washing and vancomycin could ameliorate the amount of apoptosis from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the infected samples with treatment still had higher amount of apoptosis than the un-infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of apoptosis, the caspase activity was upregulated in bacteria infected samples and remained high in samples with treatment (ANOVA P < 0.05). Signal transduction pathways activated by bacterial infection were assessed by co-transfection technique. After infection, the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and cyclic AMP-dependent protein kinase activities were elevated by 7.6-, 7.3-, and 3.2-fold, respectively, compared to the uninfected controls. The data support the hypothesis that human chondrocytes will undergo apoptosis after infection by a single organism. Apoptosis and activated intracellular kinase activities may be related to the pathogenesis of post-infectious destructive arthropathy.
authors.affiliation: Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. bone@doctor.com
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: C Y
authors.initials: CY
authors.lastname: Yen
authors.forename: S W
authors.initials: SW
authors.lastname: Ueng
authors.forename: C H
authors.initials: CH
authors.lastname: Shih
authors.forename: C C
authors.initials: CC
authors.lastname: Chao
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology* / Q000382:microbiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013203:Staphylococcal Infections / Q000503:physiopathology*
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases