Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes

Hoff, Paula; Buttgereit, Frank; Burmester, Gerd‐Rüdiger; Jakstadt, Manuela; Gaber, Timo; Andreas, Kristin; Matziolis, Georg; Perka, Carsten; Röhner, Eric

doi:10.1007/s00264-012-1724-1

Cited by 89 publications

(75 citation statements)

References 23 publications

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“…These studies have demonstrated the enhanced production of key inflammatory mediators from chondrocytes exposed to OA synovial fluid or the synovium itself, which may act to further stimulate macrophage inflammation. 12,56,57,68,69 Cumulatively, our results agree well with changes seen in early OA and with similar in vitro model systems using NCs.…”

Section: Discussionsupporting

confidence: 87%

“…For example, the expression trends for Aggrecan, Sox-9, and the MMPs are similar to previous reports by Sun et al, 28 who treated 3D encapsulated human chondrocytes with conditioned media obtained from differentiated THP-1 cells, and Peck et al, 33 who cocultured scaffold-free 3D cartilage with 2D RAW 264.7 macrophages in a trans-well setup. Similarly, the cytokine expression data are also similar to two previous reportsone in which healthy human chondrocytes were treated with the synovial fluid of OA patients, 68 and another wherein healthy cartilage explants were cocultured with synovium from OA patients. 69 Effect of coculture on AMs.…”

Section: D System To Study Effects Of Osteoarthritic Inflammationsupporting

confidence: 84%

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A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Section: Discussionsupporting

confidence: 87%

Section: D System To Study Effects Of Osteoarthritic Inflammationsupporting

confidence: 84%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

View full text Add to dashboard Cite

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“…According to previous findings that certain pro-inflammatory cytokines, such as IL-6, may cause or intensify psychological symptoms [27], these results suggest that high levels of inflammation due to injury may be a risk factor for post trauma psychological symptomatology. Other studies described other conditions with significant levels of various cytokines in the synovial fluid of patients with rheumatoid arthritis and also in patients with osteoarthritis, supporting a pro-inflammatory process in the pathogenesis of osteoarthritis [28][29][30]. Elevated plasma levels of proinflammatory cytokines, such as IL-1beta, IL-8 and TNFalpha, were also observed as useful markers of bone resorption in patients with aseptic loosening of large joint prosthesis [31].…”

Section: Discussionmentioning

confidence: 86%

Cytokine Levels (IL-4, IL-6, IL-8 and TGFβ) as Potential Biomarkers of Systemic Inflammatory Response in Trauma Patients

Volpin

Cohen

Assaf

et al. 2014

International Orthopaedics (SICOT)

105

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Purpose Much research is now being conducted in order to understand the role of cytokines in the development of the inflammatory response following trauma. The purpose of this study was to evaluate whether serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma. Methods We conducted a prospective study with 71 individuals of whom 13 (18.3 %) were healthy controls and 58 (81.7 %) were traumatized orthopaedic patients who were categorized into two groups: 31 (43.6 %) with moderate injuries and 27 (38.1 %) patients with severe orthopaedic trauma. Thirty cc of heparinized blood were drawn from each individual within a few hours after the injury. Serum levels of pro-inflammatory, regulatory and anti-inflammatory cytokines were measured in each individual participant.

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“…First, leptin appears to be a mediator of the immuno-inflammatory response in different experimental models. The proinflammatory cytokine-like functions of leptin in OA [10,[44][45][46][47] could explain its role in peripheral sensitization. Second, animal models suggest an involvement of leptin in the pathogenesis of pain at the spinal level and a possible role in the development of neuropathic pain [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Do synovial leptin levels correlate with pain in end stage arthritis?

Lübbeke

Finckh

Puskás

et al. 2013

International Orthopaedics (SICOT)

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Purpose We evaluated whether synovial fluid (SF) leptin concentrations correlate with pain severity in patients with hip or knee endstage osteoarthritis (OA) and whether they mediate the association between increased joint pain and (1) female gender and (2) obesity. Methods We conducted a cross-sectional study including patients with primary hip and knee OA undergoing joint replacement between January and December 2010. SF leptin concentrations obtained on the day of surgery were assessed. Main outcome was pain severity measured pre-operatively using WOMAC and VAS pain scales. Results A total of 219 patients were included, 123 hip and 96 knee arthroplasties. Mean age was 72 years, 59 % were women. Mean SF leptin levels were 22.9 (±25.6) ng/ml in women and 5.4 (±5.9) ng/ml in men. Levels >19.6 ng/ml (highest quartile) were significantly associated with increased pain on both WOMAC (mean difference −9.6, 95 % CI −15.1 to −4.0) and VAS scale (mean difference 0.8, 95 % CI 0.2-1.3). Associations remained unchanged after adjusting for age, co-morbidities, contra-lateral arthritic joint, OA site, and disability. The associations observed between increased pain and female gender or obesity were substantially reduced after adjusting for SF leptin. Conclusion Joint pain is associated with SF leptin concentrations. Increased pre-operative pain observed in women and obese may be related to high intra-articular leptin levels.

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Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes

Cited by 89 publications

References 23 publications

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Cytokine Levels (IL-4, IL-6, IL-8 and TGFβ) as Potential Biomarkers of Systemic Inflammatory Response in Trauma Patients

Do synovial leptin levels correlate with pain in end stage arthritis?

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