AB0090 Verbascoside and hydroxytyrosol downregulate stress-related pathways in human osteoarthritic articular chondrocytes

Elmazoğlu, Zübeyir; Çolakoğlu, Muhammed Kadri; Banerjee, Sreeparna; Bıtık, Berivan; Aktekin, Cem Nuri; Göker, Berna; Karasu, Çi̇men

doi:10.1136/annrheumdis-2018-eular.7038

Cited by 4 publications

(8 citation statements)

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“…In accordance with the findings of our preliminary studies (Elmazoglu et al, 2018(Elmazoglu et al, , 2020Goker et al, 2018) and other laboratories (Charlier et al, 2016;Hardin et al, 2015;Lepetsos et al, 2019;Portal-Nunez et al, 2016) (Lepetsos et al, 2019;Sun et al, 2017). In the present study, OACs at p0-1 showed a higher pJNK/JNK ratio and excessive ROS production than OACs at p2-3<, supporting the notion that the interaction between ROS and JNK plays a distinctive role in OA pathology.…”

Section: Discussionsupporting

confidence: 92%

“…The microelectronic biosensor iCELLigence Real Time Cell Analysis System® (RTCA, ACEA Biosciences, San Diego, CA, USA) was used to measure impedance when cells adhere to the microelectrodes causing an alternating current (Elmazoglu et al, 2018(Elmazoglu et al, , 2020. This new concept has just emerged as an interesting method based on the use of culture plates (E-Plates) with gold microelectrodes in their base.…”

Section: Measurement Of Cell Impedance By Icelligencementioning

confidence: 99%

“…ELISAs for LPO, HNE, AGE, GPx, GM-CSF, caspase-1/ICE, and p-JNK/JNK ) end product-protein adducts (AGE-adduct), glutathione peroxidase (GPx), caspase-1/interleukin-1 converting enzyme (ICE), granulocyte-macrophage colony-stimulating factor (GM-CSF), and c-Jun N-terminal kinases (p-JNK (pThr183/Tyr185)/ pan-JNK), in the lysates were measured by ELISA kits according to the manufacturer's instructions after 24 h incubation with the different concentrations of the polyphenolic agents or ibuprofen. Results were normalized with their protein concentrations and expressed as the relative percentages of control group (OACs) or according to kits own standard-curve graphs (Elmazoglu et al, 2018(Elmazoglu et al, , 2020Goker, Elmazoglu, Bitik, Aktekin and Karasu, 2018)…”

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confidence: 99%

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TLR4, RAGE, and p‐JNK/JNK mediated inflammatory aggression in osteoathritic human chondrocytes are counteracted by redox‐sensitive phenolic olive compounds: Comparison with ibuprofen

Elmazoğlu

Bek

Saribas

et al. 2020

J Tissue Eng Regen Med

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Osteoarthritic chondrocytes show an over‐activity of inflammatory catabolic mediators, and olive products have attracted attention because they were discovered to have some benefits on osteoarthritis patients. We investigated the mechanisms of action of olive leaf polyphenolic compounds in osteoarthritic chondrocytes (OACs) using a standardized leaf extract, ZeyEX, and its main phenolic component, oleuropein, also compared with anti‐inflammatory drug ibuprofen. OACs, isolated from joint‐cartilages of Grade 4 OA patients, were found to express COMP and MMP‐9 throughout their culture period. ZeyEX, oleuropein, and ibuprofen increased cell viability at concentrations of 1–100 nM, did not change at 500 nM–50 μM, but inhibited at ≥100 μM. The adherence profile of OACs increased with 1 μM of ibuprofen or ZeyEX and 10 nM–1 μM oleuropein. Although the markers for oxidative and nitrosative stresses (ROS and 3‐NT) generally inhibited by three agents, the inhibitory effect of ZeyEX on 3‐NT emerged dramatically (1 nM–10 μM). Lipid‐hydroperoxides and HNE‐adducts were also inhibited by each agent, but AGE‐adducts unchanged by oleuropein while reduced by ZeyEX and ibuprofen. Inflammatory biomarkers, IL‐1β, IL‐6, Casp‐1/ICE, and TNF‐α, were inhibited by three agents, however osteopontin and GM‐CSF by only ZeyEX and ibuprofen. A decreased COMP, TLR4, and RAGE expression levels were observed by three agents, but only the effects of ZeyEX was concentration‐dependent. In particular, ZeyEX and oleuropein improved COL2, inhibited p‐JNK/JNK, and increased GPx. COX2 was only inhibited by ibuprofen. The results indicate that polyphenolic‐olive compounds counteract redox‐sensitive inflammatory aggressions in osteoarthritic chondrocytes that may stop the progression of pathology and allow regeneration.

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Section: Discussionsupporting

confidence: 92%

Section: Measurement Of Cell Impedance By Icelligencementioning

confidence: 99%

mentioning

confidence: 99%

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TLR4, RAGE, and p‐JNK/JNK mediated inflammatory aggression in osteoathritic human chondrocytes are counteracted by redox‐sensitive phenolic olive compounds: Comparison with ibuprofen

Elmazoğlu

Bek

Saribas

et al. 2020

J Tissue Eng Regen Med

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“…After biologics treatment, Rooney's score in RL group and M group were 10. 4 4 The alterations in cell counts, viability (MTT, NRU), proliferation (RTCA-iCELLigence System), reactive oxygen species (ROS) generation, stress-related signalling proteins and inflammatory progenitors ICE/caspase-1 (ELISA) were determined. Results: Cell viability was increased at lower concentrations of hydroxytyrosol in OA chondrocytes (P1, 30th day).…”

Section: Discussionmentioning

confidence: 99%

AB0087 Synovial tissue macrophages polarisation (M1, M2) in patients with undifferentiated arthritismeeting diagnostic criteria for rheumatoid arthritis or psoriatic arthritis along the follow up

Aguilera

Fuentelsaz-Romero²,

Estrada-Capetillo³

et al. 2018

Cartilage, Synovium and Bone

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BackgroundUndifferentiated arthritis (UA) is defined as an inflammatory oligo-or polyarthritis that does not fulfil criteria for a definitive diagnosis. Earlier diagnosis would permits a better functional prognosis. Synovial tissue (ST) macrophages have been associated with disease activity, radiographic erosion and response to therapy in RA. Furthermore, it has been reported that M1 polarised macrophages predominate in RA synovitis, whereas M2 predominate in SpA synovitis.1 ObjectivesTo analyse polarised macrophages (M1 proinflammatory and M2 anti-inflammatory) in ST of patients with UA which evolved to RA or PsA, after a long follow-up, to explore their diagnostic value.MethodsTo determine the polarisation state of macrophages in ST obtained by arthroscopy from patients with UA that evolved to RA (UA-RA=8) or PsA (UA-PsA=9), the expression of proteins associated to GM-CSF-driven polarisation M1(INHBA, TNFα and MMP12) and M-CSF-driven polarisation M2(CD209) was assessed in ST CD163+macrophages. Patients with established RA(n=12) or PsA(n=10) were included as control. 4 µm cryosections of ST in OCT were blocked for 10 min with 1% human immunoglobulins and incubated with primary (1–5 µg/ml) and secondary antibodies. Imaging was performed with an inverted confocal microscope (SPE, Leica Microsystems) and glycerol immersion objective (ACS-APO 20x/NA 0.60). Single cell mean fluorescence intensity(MFI) was assessed using ImageJ software (National Institutes of Health, Bethesda, MD, USA). At least three random fields were evaluated for each type of ST, quantifying the expression of INHBA, TNF-α, MMP12 and CD209 in all segmented CD163+macrophages. Macrophages density was normalised based on selected tissue area(mm2). After background subtraction, data were plotted using GraphPad software (GraphPad Software, La Jolla, CA, USA).ResultsCD163+ sublining (SL) macrophages from UA-RA expressed abundantly the INHBA-encoded activin A, whereas TNFα and MMP12 were variably detected. Regarding the M-CSF-associated marker CD209, 2 populations of CD163+ macrophages were found in the SL of UA-RA, CD163+CD209+ and the other CD163+CD209-, with higher than 100 arbitrary units (au) for CD163+CD209+ and lower than 100 au for CD163+CD209-. Similarly, INHBA, MMP12 and TNFα expression and 2 populations of CD209 were detected in CD163+ macrophages from UA-PsA. Macrophage density was also found comparable between UA, with 650/mm2 in UA-RA and 649/mm2 in UA-PsA. Quantification of the above indicated markers in CD163 +ST macrophages from established RA and PsA revealed similar levels of INHBA, TNFα, MMP12 and CD209 than those from UA-RA and UA-PsA.ConclusionsThis study shows for the first time that the polarisation state of ST CD163+ macrophages in UA progressing to RA and PsA is similar to that of established RA and PsA in terms of INHBA, MMP12, TNFα and CD209 expression. Therefore, the inflammatory polarisation state of macrophages is similar in RA and PsA and it is already detected at the earlier steps.Reference[1] Vandooren B, et al. Arthritis...

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“…İSM.4.06.68.49), as described previously. 4 The alterations in cell counts, viability (MTT, NRU), proliferation (RTCA-iCELLigence System), reactive oxygen species (ROS) generation, stress-related signalling proteins and inflammatory progenitors ICE/caspase-1 (ELISA) were determined. Results: Cell viability was increased at lower concentrations of hydroxytyrosol in OA chondrocytes (P1, 30th day).…”

Section: Discussionmentioning

confidence: 99%

AB0089 Histopathological change caused by biological treatment in rheumatoid arthritis synovial tissue

Kubota

Suguro

Nakajima

et al. 2018

Cartilage, Synovium and Bone

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BackgroundMultiple studies addressing the effects of biologics on the synovial tissue in rheumatoid arthritis (RA) patients have been reported. There are, however, few studies comparing histopathological changes in the synovial tissue in the same RA patients between before and after biologics treatment.ObjectivesWe examined biologics impacts on RA synovial tissues based on pathological findings in them collected during surgeries for the same patient before and after biological drug usage.MethodsSynovial tissues were collected from 34 RA joints before and after biologics. The average age and disease duration of the study subjects were 64.0 and 22.5, respectively. Synovial tissues were evaluated by hematoxylin. Histopathological changes in the synovial tissues were compared based on Rooney’s score, and presence or absence of fibrinoid degeneration and proliferation of villi in the subsynovial tissue. We examined correlation between pathological findings in RA synovium and disease activity under biologics. Disease activity was assessed by CDAI. We examined the Histopathological changes in the Remission, Low disease activity group (RL group) and Moderate disease activity (M group). Etanercept, Infliximab, Tocilizumab, Adalimumab and Abatacept was used as biological drug for 18, 6, 5, 3 and 2 joints respectively.ResultsRooney score between before and after biological usage improved from 28.4 to 12.0 showing significant difference. Significant improvement in Rooney score was observed in all items. Fibrinoid degeneration was observed in 29 cases (85.3%) and 6 cases (17.6%) before and after biologics treatment, respectively, demonstrating a significant reduction with biologics treatment. Proliferation of villi was observed in 32 cases (94.1%) and 11 (32.4%) before and after biologics treatment, respectively, demonstrating a significant reduction with biologics treatment. After biologics treatment, Rooney’s score in RL group and M group were 10.4 and 15.3, respectively, showing a statistically significant difference. In addition, the M group had significantly higher scores in lymphoid follicle and lymphocyte infiltration compared to the RL group.ConclusionsThe study results demonstrated that biologics treatment significantly ameliorated inflammatory changes in the synovial lining layers and sublining layers. In addition, the results suggested that histopathological findings in the sublining layers reflected disease activity.Disclosure of InterestNone declared

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AB0090 Verbascoside and hydroxytyrosol downregulate stress-related pathways in human osteoarthritic articular chondrocytes

Cited by 4 publications

References 3 publications

TLR4, RAGE, and p‐JNK/JNK mediated inflammatory aggression in osteoathritic human chondrocytes are counteracted by redox‐sensitive phenolic olive compounds: Comparison with ibuprofen

TLR4, RAGE, and p‐JNK/JNK mediated inflammatory aggression in osteoathritic human chondrocytes are counteracted by redox‐sensitive phenolic olive compounds: Comparison with ibuprofen

AB0087 Synovial tissue macrophages polarisation (M1, M2) in patients with undifferentiated arthritismeeting diagnostic criteria for rheumatoid arthritis or psoriatic arthritis along the follow up

AB0089 Histopathological change caused by biological treatment in rheumatoid arthritis synovial tissue

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