The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment

Abstract. The aim of this in vitro study was to examine the possible effect of [2-methyl-5-(4-methylsulphonyl)phenyl-1-phenyl-3-(2-n-propyloxyethyl)]-1H-pyrrole (VA441), a new selective cyclooxygenase (COX)-2 inhibitor, on human osteoarthritic (OA) chondrocyte cultivated in the presence or absence of interleukin-1β (IL-1β). In particular, we assessed the effects of 1 and 10 μM of VA441, celecoxib, and indomethacin on cell viability, COX-2 and inducible nitric oxide synthase (iNOS) gene expression, prostaglandin E 2 (PGE 2 ) production, and nitric oxide (NO) and metalloproteinase-3 (MMP-3) release. Furthermore, we carried out morphological assessment by transmission electron microscopy (TEM). The presence of IL-1β led to a significant increase in PGE 2 , MMP-3, and NO production, as well as a significant increase in gene expression of COX-2 and iNOS. All the drugs tested had a statistically significant inhibitory effect on PGE 2 production and gene expression of COX-2 stimulated by IL-1β. VA441 and celecoxib significantly suppressed IL-1β-stimulated MMP-3 and NO and iNOS gene expression in a dose-dependent manner, while indomethacin did not show any significant effect on MMP-3 and NO production or on iNOS gene expression. TEM demonstrated that IL-1β severely alters the structure of chondrocytes; after coincubation with VA441 or celecoxib, the cells recovered their ultrastructure. Our data suggest that VA441 and celecoxib may have a beneficial effect on chondrocyte metabolism.

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“…Our data confirm the possible chondroprotective role of a COX-2 selective inhibitor in agreement with other authors (14,16,24,40,46,47,51,52).…”

Section: Discussionsupporting

confidence: 93%

In Vitro Effects of VA441, a New Selective Cyclooxygenase-2 Inhibitor, on Human Osteoarthritic Chondrocytes exposed to IL-1^|^beta;

Fioravanti¹,

Tinti²,

Pascarelli³

et al. 2012

J Pharmacol Sci

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“…We reported the anti-inflammatory role of morin on OA through suppressing inflammatory mediator production. Previous studies showed that some COX-2 selective inhibitors could also inhibit inflammatory cytokine-induced inflammatory response and cartilage damage [6,23]. These results showed that VA694, Naproxcinod and Naproxen could inhibit IL-1β-induced inflammatory response by attenuating NF-κB activation [24].…”

Section: Discussionmentioning

confidence: 84%

Morin Exhibits Anti-Inflammatory Effects on IL-1β-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway

Wang

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteoarthritis (OA) is a multifactorial disease that is associated with inflammation in joints. The purpose of the present study was to investigate the anti-inflammatory activity and mechanism of morin on human osteoarthritis chondrocytes stimulated by IL-1β. Methods: The levels of NO and PGE2 were measured by the Griess method and ELISA. The levels of MMP1, MMP3, and MMP13 were also measured by ELISA. Results: The results revealed that IL-1β significantly increased the production of NO, PGE2, MMP1, MMP3, and MMP13. Additionally, the increases were significantly attenuated by treatment with morin. Furthermore, IL-1β-induced NF-κB activation was suppressed by morin. In addition, the expression of Nrf2 and HO-1 were increased by morin and knockdown of Nrf2 could prevent the anti-inflammatory effects of morin. Conclusion: In conclusion, this study suggested that morin attenuated IL-1β-induced inflammation by activating the Nrf2 signaling pathway.

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“…In a trial (LOE IIb), patients who were candidates for total knee replacement (TKR) surgery were treated either with celecoxib or indomethacin for a four-week period prior to the procedure, and cartilage and synovial samples were evaluated after the surgery. [61] Proteoglycan synthesis was found to be significantly increased among celecoxib users but not in the indomethacin and control groups. Prostaglandin E 2 (PGE 2) levels were found to be lower in the patients who used either of the drugs when compared with the controls.…”

Section: Pharmacologic Treatmentmentioning

confidence: 89%

Evidence-Based Recommendations for the Management of Knee Osteoarthritis: A Consensus Report of the Turkish League Against Rheumatism

et al. 2012

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Amaç: Diz osteoartriti (OA) sık görülen ve neden olduğu ağrı ve sakatlık sonucunda sosyoekonomik yük bindiren bir hastalıktır. Türkiye Romatizma Araştırma ve Savaş Derneği (TRASD) OA tedavisi ile uğraşan hekimlere günlük klinik uygulamalarında yardımcı olmak amacıyla, uzman görüşleri ile desteklenmiş, ulusal "diz osteoartrit tedavisinde kanıta dayalı önerileri" hazırlamak için bir proje başlatmıştır. Objectives: Knee osteoarthritis (OA) is a common disease which causes pain, disability and great socioeconomic burden as a result. Turkish League Against Rheumatism (TLAR) initiated a project to prepare national, "evidence-based recommendations for the management of knee osteoarthritis" supported by expertopinion in order to assist the physicians who are interested in knee OA in their daily clinical practice. Gereç ve yöntemler: Materials and methods:The expert committee was composed of 25 academicians, 23 of whom were physical medicine and rehabilitation (PM&R) specialists (three also had rheumatology subspeciality) and two were orthopedic surgeons. At the first meeting, the previous guidelines were discussed, and 2008 Osteoarthritis Research Society International (OARSI) recommendations were decided to be taken as the fundamental template for national recommendations. Databases of the Pubmed, Embase, Cochrane, and Turkish Medical Index were used to search the literature, and this was carried out for the period between 2009-2010 for international publications since studies up to 2009 were present in the 2010 OARSI update. No limit was applied for searching of national publications. The selected relevant publications were graded according to evidence level and quality, and were sent to the members who were then asked to suggest propositions according to their experiences, knowledge, and review of the literature. After amalgamation and editing of new proposals, Delphi rounds were started. After five Delphi rounds, the propositions on which the members were in consensus, were discussed with regard to evidence and the "strength of recommendation" was determined by measuring on visual analog scale (VAS) for each proposal at the final meeting.Results: Nineteen propositions (one for general principles, nine for nonpharmacologic treatments, seven for pharmacologic treatments, and two for surgical treatments) were accepted as the "TLAR Evidence-Based Recommendations for the Management of Knee OA" in consensus as a result of Delphi rounds. Conclusion:Evidence-based recommendations for the management of knee OA were developed by TLAR for the first time in our country. The recommendations should be updated regularly according to new evidence and insights. It is expected that physicians who are interested in knee OA will benefit greatly from this report in their daily clinical practice.

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The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment

Abstract: Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.

Cited by 69 publications

References 33 publications

In Vitro Effects of VA441, a New Selective Cyclooxygenase-2 Inhibitor, on Human Osteoarthritic Chondrocytes exposed to IL-1^|^beta;

In Vitro Effects of VA441, a New Selective Cyclooxygenase-2 Inhibitor, on Human Osteoarthritic Chondrocytes exposed to IL-1^|^beta;

Morin Exhibits Anti-Inflammatory Effects on IL-1β-Stimulated Human Osteoarthritis Chondrocytes by Activating the Nrf2 Signaling Pathway

Evidence-Based Recommendations for the Management of Knee Osteoarthritis: A Consensus Report of the Turkish League Against Rheumatism

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