Induced Apoptosis of Chondrocytes by Porphyromonas gingivalis as a Possible Pathway for Cartilage Loss in Rheumatoid Arthritis

Abstract

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.

Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by inhibiting proteoglycan loss and chondrocyte apoptosis in rats with collagen-induced arthritis

“…Recently, rheumatologists have begun to notice the role of cell apoptosis in the process of cartilage destruction in RA (Kim and Song 1999;Rohner et al 2010;Yatsugi et al 2000;Hilbers et al 2003). Nevertheless, the regulating mechanisms of chondrocyte apoptosis in the progression and treatment of RA have not been fully elucidated as yet.…”

Mechanisms of Immunological Tolerance Disruption

“…Тре-тья группа связывается перекрестной связью с двумя цепями MHC II класса (энтеротоксин A S. aureus) [Fraser, Proft, 2008]. Эти данные по суперантигенам представляют интерес в связи с тем, что бактериальные или вирусные инфек-ции обнаруживаются у большинства больных АИЗ, в частности РА: P. gingivalis [Martinez-Mar-Martinez-Mar--Mar-Martinez et al, Röhner et al, 2010], EBV [Klatt et al, 2005;Erre et al, 2015], CMV [Pierer et al, 2012;Mohammad et al, 2014]. В ряде работ было показано, что иммунизация с P. gingiva-.…”

Toxicity of antiseptics against chondrocytes: What is best for the cartilage in septic joint surgery?

“…Chondrocyte isolation was performed as described before [13]. Cartilage was obtained from human donors with knee osteoarthritis not presenting any evidence of sepsis.…”