title: Mycoplasma synoviae induces upregulation of apoptotic genes, secretion of nitric oxide and appearance of an apoptotic phenotype in infected chicken chondrocytes.
abstract: The role of chondrocytes in the development of infectious arthritis is not well understood. Several examples of mycoplasma-induced arthritis in animals indicate that chondrocytes come into direct contact with bacteria. The objective of this study was to analyze the interaction of an arthrogenic Mycoplasma synoviae strain WVU 1853 with chicken chondrocytes. We found that M. synoviae significantly reduces chondrocyte respiration. This was accompanied by alterations in chondrocyte morphology, namely cell shrinkage and cytoplasm condensation, as well as nuclear condensation and formation of plasma membrane invaginations containing nuclear material, which appeared to cleave off the cell surface. In concordance with these apoptosis-like events in chondrocytes, transcription was increased in several pro-apoptotic genes. Twenty-four hours after infection, strong upregulation was assayed in NOS2, Mapk11, CASP8 and Casp3 genes. Twenty-four and 72 h incubation of chondrocytes with M. synoviae induced upregulation of AIFM1, NFκB1, htrA3 and BCL2. Casp3 and NOS2 remained upregulated, but upregulation ceased for Mapk11 and CASP8 genes. Increased production of nitric oxide was also confirmed in cell supernates. The data suggests that chicken chondrocytes infected with M. synoviae die by apoptosis involving production of nitric oxide, caspase 3 activation and mitochondrial inactivation. The results of this study show for the first time that mycoplasmas could cause chondrocyte apoptosis. This could contribute to tissue destruction and influence the development of arthritic conditions. Hence, the study gives new insights into the role of mycoplasma infection on chondrocyte biology and development of infectious arthritis in chickens and potentially in humans.
authors.affiliation: University of Ljubljana, Department of Animal Science, Chair for Genetics, Animal Biotechnology and Immunology, Groblje 3, 1230 Domzale, Slovenia. Daliborka.Dusanic@bf.uni-lj.si.
authors.forename: Daliborka
authors.initials: D
authors.lastname: Dusanic
authors.forename: Dusan
authors.initials: D
authors.lastname: Bencina
authors.forename: Irena
authors.initials: I
authors.lastname: Oven
authors.forename: Ivanka
authors.initials: I
authors.lastname: Cizelj
authors.forename: Mojca
authors.initials: M
authors.lastname: Bencina
authors.forename: Mojca
authors.initials: M
authors.lastname: Narat
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002645:Chickens; D019902:Chondrocytes / Q000166:cytology* / Q000382:microbiology; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D018613:Microscopy, Confocal / Q000662:veterinary; D008856:Microscopy, Fluorescence / Q000662:veterinary; D008858:Microscopy, Phase-Contrast / Q000662:veterinary; D009175:Mycoplasma Infections / Q000235:genetics / Q000382:microbiology / Q000662:veterinary*; D045805:Mycoplasma synoviae / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D011201:Poultry Diseases / Q000235:genetics* / Q000382:microbiology; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors
chemical_list: D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D009569:Nitric Oxide