Chromosomal DNA from a variety of bacterial species is present in synovial tissue from patients with various forms of arthritis

Gérard, Hervé C.; Wang, Zhao; Wang, Geng Feng; El-Gabalawy, Hani; Goldbach-Mansky, Rafaela; Li, Yong; Majeed, Warqaa; Zhang, Haidi; Ngai, Ngayin; Hudson, Alan P.; Schumacher, H. Ralph

doi:10.1002/1529-0131(200107)44:7<1689::aid-art293>3.0.co;2-k

Cited by 94 publications

(53 citation statements)

References 27 publications

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“…High percentage of bacterial DNA was detected in the RA and reactive arthritis patients. 161 In addition, bacterial peptideglycans was demonstrated in the synovial macrophages. 162 Exogenous PAMPs can evoke initial immune response via TLRs, which has been implicated to be involved in triggering of joint inflammation and disease flares in RA.…”

Section: Pamps and Damps In Ra Synovial Tissuesmentioning

confidence: 99%

Toll-like Receptor

Takagi

2011

J Clin Exp Hematopathol

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Toll like receptor (TLR), one of the key functions of innate immune system, can recognize not only exogenous pathogenassociated molecular patterns, namely PAMPs, but also endogenous molecules created upon tissue injury, sterile inflammation and degeneration. Endogenous TLR ligands are called as damage-associated molecular patters (DAMPs), including endogenous molecules released by activated and necrotic cells, and extracellular matrix molecules. DAMPs are also known as alarmins. TLR research has brought about new insights in the rheumatic diseases. Previous reports suggest that TLRs and the signal pathways intensively contribute to the pathogenesis of rheumatoid arthritis (RA) and other arthritic conditions with interaction of various TLR ligands. Accumulated knowledge of TLR system is summarized to overlook TLRs and the signaling pathway in arthritis conditions, with special reference to RA. 〔J Clin Exp Hematopathol 51(2) : 77-92, 2011〕

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Section: Pamps and Damps In Ra Synovial Tissuesmentioning

confidence: 99%

Toll-like Receptor

Takagi

2011

J Clin Exp Hematopathol

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“…PostSalmonella ReA can be accompanied by erosive sacroiliitis (13). Despite the strong temporal association with antecedent infection, the pathogenesis of ReA is not resolved, but there is strong evidence of local persistence of microbial antigens (6) and microbial nucleic acids (4). Bacterial LPS has been detected in neutrophils and macrophages for prolonged periods after the inciting infection, although synovial fibroblasts were not specifically examined (5).…”

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confidence: 99%

Synovial Fibroblasts Infected with Salmonella enterica Serovar Typhimurium Mediate Osteoclast Differentiation and Activation

et al. 2004

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The mechanisms whereby arthritogenic organisms may induce cartilage and bone erosions in infectiontriggered arthritis remain unknown. In this study, we asked whether an arthritogenic organism could contribute to osteoclast differentiation and activation through regulation of the receptor activator of NF-B ligand (RANKL) in synovial fibroblasts. Rat synovial fibroblasts were infected in vitro with Salmonella enterica serovar Typhimurium and monitored over time. The expression of RANKL in resting and infected synovial fibroblasts was quantified by reverse transcription-PCR and Western blotting. Osteoclast progenitors, isolated from femurs of 8-week-old rats and cultured in the presence of macrophage colony-stimulating factor, were cocultured with either infected or noninfected synovial fibroblasts for 2 to 4 days. Differentiation and maturation of osteoclasts were determined by morphology and tartrate-resistant acid phosphatase (TRAP) staining and by a bone resorption bioassay. RANKL expression was undetectable in resting synovial fibroblasts but was dose-dependently upregulated in cells after Salmonella infection. Osteoprotegerin was constitutively expressed by synovial fibroblasts and was not upregulated by infection. Further, we observed the formation of multinucleated TRAP-positive cells and formation of bone resorption pits in cocultures of bone marrow-derived osteoclast precursors with synovial fibroblasts infected with Salmonella but not with heat-killed Salmonella or noninfected cells. Arthritogenic bacteria may alter bone structure via synovial fibroblast intermediaries, since infected synovial fibroblasts (i) upregulate RANKL expression and (ii) enhance osteoclast precursor maturation into multinucleated, TRAP-positive, bone-resorbing, osteoclast-like cells. These data provide a link between infection and osteoclastogenesis. A better understanding of infection-mediated osteoclast differentiation and activation may provide new therapeutic strategies for inflammatory joint disease.

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“…Furthermore, in the same study M13 sequences in spleen were found to be integrated into mouse chromosomal DNA. In humans, it is well established that gut-derived bacterial antigens and DNA can be detected in the peripheral blood and may accumulate in joints (12,34,35). Clearance of this material from joints may be less efficient in patients with inflammatory disease.…”

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confidence: 99%

Novel Endogenous Retrovirus in Rabbits Previously Reported as Human Retrovirus 5

Griffiths

Voisset

Venables³

et al. 2002

J Virol

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Human retrovirus 5 (HRV-5) represented a fragment of a novel retrovirus sequence identified in human RNA and DNA preparations. In this study, the genome of HRV-5 was cloned and sequenced and integration sites were analyzed. Using PCR and Southern hybridization, we showed that HRV-5 is not integrated into human DNA. A survey of other species revealed that HRV-5 is present in the genomic DNA of the European rabbit (Oryctolagus cuniculus) and belongs to an endogenous retrovirus family found in rabbits. The presence of rabbit sequences flanking HRV-5 proviruses in human DNA extracts suggested that rabbit DNA was present in our human extracts, and this was confirmed by PCR analysis that revealed the presence of rabbit mitochondrial DNA sequences in four of five human DNA preparations tested. The origin of the rabbit DNA and HRV-5 in human DNA preparations remains unclear, but laboratory contamination cannot explain the preferential detection of HRV-5 in inflammatory diseases and lymphomas reported previously. This is the first description of a retrovirus genome in rabbits, and sequence analysis shows that it is related to but distinct from A-type retroelements of mice and other rodents. The species distribution of HRV-5 is restricted to rabbits; other species, including other members of the order Lagomorpha, do not contain this sequence. Analysis of HRV-5 expression by Northern hybridization and reverse transcriptase PCR indicates that the virus is transcribed at a low level in many rabbit tissues. In light of these findings we propose that the sequence previously designated HRV-5 should now be denoted RERV-H (for rabbit endogenous retrovirus H).

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Chromosomal DNA from a variety of bacterial species is present in synovial tissue from patients with various forms of arthritis

Cited by 94 publications

References 27 publications

Toll-like Receptor

Toll-like Receptor

Synovial Fibroblasts Infected with Salmonella enterica Serovar Typhimurium Mediate Osteoclast Differentiation and Activation

Novel Endogenous Retrovirus in Rabbits Previously Reported as Human Retrovirus 5

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