Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis.
The role of bacterial infections in the pathogenesis of rheumatoid arthritis (RA) has gained increasing interest. Patients with RA often exhibit periodontal disease, which is associated with pathogens like Porphyromonas gingivalis. The present study examines the direct effects of P. gingivalis on apoptosis of human chondrocytes (a feature of inflammatory joint diseases) as one can assume an interrelation of pathogenesis of RA and P. gingivalis infections. Primary chondrocytes were infected with P. gingivalis. Early apoptotic and dead cell analysis was performed using Annexin-V, 7AAD, and propidium iodide and examined by flow cytometry and fluorescence microscopy. Caspase activation and DNA fragmentation were determined by western blot analysis and TUNEL reaction. Flow cytometry and fluorescence microscopy demonstrated an increase of Annexin-V-positive early apoptotic chondrocytes after infection. Western blot showed upregulation of activated caspase-3 expression, and TUNEL reaction revealed considerable DNA fragmentation following infection. The data show that P. gingivalis promotes early and later stages of apoptosis of primary human chondrocytes, which might contribute to the joint damage seen in the pathogenesis of RA.
Röhner
E
E
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany. eric.roehner@charite.de
Detert
J
J
Kolar
P
P
Hocke
A
A
N'Guessan
P
P
Matziolis
G
G
Kanitz
V
V
Bernimoulin
J P
JP
Kielbassa
A
A
Burmester
G R
GR
Buttgereit
F
F
Pischon
N
N
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D016866:Bacteroidaceae Infections / Q000473:pathology*; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000382:microbiology / Q000473:pathology*; D053148:Caspase 3 / Q000096:biosynthesis; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008856:Microscopy, Fluorescence; D016966:Porphyromonas gingivalis / Q000502:physiology*
D017304:Annexin A5; D053148:Caspase 3