Dataset Information

Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation.

ABSTRACT: The microbiome is recognized as a new frontier in medicine with connections to a variety of diseases. We aimed to evaluate the association of lipopolysaccharide (LPS), a key pro-inflammatory product of the microbiome, with severity of inflammation, symptoms and radiographic abnormalities of knee osteoarthritis (OA).LPS was measured using a recombinant Factor C (rFC) assay, carefully optimized for systemic and synovial fluid (SF) analyses. LPS binding protein (LBP) was tested in both serum and SF of 25 patients (31 knees) from the Etarfolatide cohort for association with OA phenotypic outcomes. Models were adjusted for age, gender and body mass index.Based on LPS spike-and-recovery, both serum and SF dilutions of 0.1% were required to achieve recovery rates of at least 75% in all test specimens. Low coefficients of variation (CVs) (<10%) were achieved with both serum and SF dilutions <0.2%. Serum LPS and LBP were associated with the abundance of activated macrophages in the knee joint capsule and synovium. SF LPS and LBP were associated with the abundance of activated macrophages in the synovium. Serum LPS, LBP and SF LPS were associated with knee osteophyte severity. SF LPS was positively associated with knee joint space narrowing (JSN) severity and total WOMAC score. SF LBP was positively associated with self-reported knee pain score.These data strongly support a role for LPS in the pathogenesis and severity of structural abnormalities and symptoms of knee OA.

SUBMITTER: Huang ZY

PROVIDER: S-EPMC5026878 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation.

Huang Z Y ZY Stabler T T Pei F X FX Kraus V B VB

Osteoarthritis and cartilage 20160520 10

<h4>Objective</h4>The microbiome is recognized as a new frontier in medicine with connections to a variety of diseases. We aimed to evaluate the association of lipopolysaccharide (LPS), a key pro-inflammatory product of the microbiome, with severity of inflammation, symptoms and radiographic abnormalities of knee osteoarthritis (OA).<h4>Design</h4>LPS was measured using a recombinant Factor C (rFC) assay, carefully optimized for systemic and synovial fluid (SF) analyses. LPS binding protein (LBP ...[more]

PMID: 27216281

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Project description:Retinal neurodegenerative diseases involve a scenario of inflammation and cell death that leads to morphological alterations and visual impairment. Non-ocular inflammatory processes could affect neurodegenerative retinal disorders and their progression, at least in part by activating microglial cells and releasing pro-inflammatory cytokines. Our purpose was to study the consequences of a systemic inflammatory process in the progression of retinal degeneration in P23H rats, a retinitis pigmentosa (RP) model. In order to induce a mild chronic systemic inflammation, we administered low doses of lipopolysaccharide (LPS) from age P20 to P60 to dystrophic P23H rats and healthy SD rats. Visual responsiveness was assessed by electroretinography (ERG). The morphological state of the retinas was analyzed by fluorescent immunohistochemistry (IHC), evaluating the number, morphology, and connectivity of different neuronal populations by means of cell type-specific markers. Microglia density, distribution, and degree of activation were evaluated by IHC and flow cytometry. The expression levels of inflammation- and apoptosis-related genes were analyzed by qRT-PCR arrays. Low-dose LPS administration did not induce significant functional or morphological changes in the retina of SD rats, although at the molecular level, we detected expression changes in genes related to apoptosis. Otherwise, systemic injection of LPS into P23H rats induced a further deterioration in the ERG response, with greater loss of photoreceptors and worsening of synaptic connectivity, accompanied by increasing numbers of microglial cells, which also showed a more intense activation state. Several inflammation- and apoptosis-related genes were upregulated. Our results indicate that chronic exacerbation of the inflammatory response in response to LPS accelerates neurodegeneration in dystrophic P23H rats, suggesting that in patients with ocular neurodegenerative diseases, peripheral damage, as a systemic infection or chronic inflammatory process, could accelerate disease progression, and should be taken into account in order to select an appropriate therapy to revert, block or slow-down the degenerative process.

Dataset Information

Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation.

Publications

Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation.

Similar Datasets

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