Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage

Abstract

1 Since nonsteroidal anti-in¯ammatory drugs (NSAIDs) may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan and hyaluronan (HA) molecules produced by aceclofenac, diclofenac and meloxicam in human osteoarthritic (OA) cartilage. 2 Explants were sampled from the medial femoral condyle and were classi®ed by use of the Mankin's histological-histochemical grading system. Cartilage specimens exhibited moderate (M) OA in 20 subjects and had severe (S) OA in 20. 3 Cartilage explants were pulsed with [-3H]-glucosamine and chased in the absence or in the presence of 0.3 ± 3 mg ml 71 of either aceclofenac, diclofenac or meloxicam. After papain digestion, the labelled chondroitin sulphate ([-3H]-proteoglycans) and [-3H]-HA molecules present in the tissue and media were puri®ed by anion-exchange chromatography. 4 In cartilage with MOA and SOA, the metabolic balance of proteoglycan and HA was unaected by diclofenac. In contrast, and in a dose-dependent manner, aceclofenac and meloxicam both increased the synthesis of proteoglycans and HA in explants with MOA and SOA; these two NSAIDs also reduced signi®cantly the net loss of [-3H]-proteoglycans and [-3H]-HA molecules from cartilage explants. 5 The data obtained in short-term in vitro cultures indicate that, at the concentrations found in synovial¯uid, aceclofenac and meloxicam may exert a favourable eect on the overall metabolism of proteoglycans and HA in cartilage with MOA and SOA.

In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

“…The NSAID meloxicam is a selective cyclooxygenase 2 (COX-2) inhibitor (10), with known antiinflammatory and antiangiogenic effects (11)(12)(13). NSAIDs are prescribed primarily for the management of OA pain (14,15); however, they have also been found to have positive effects on cartilage health in OA by increasing proteoglycan and hyaluronan synthesis (16). Thus, we hypothesized that the addition of an NSAID to the bisphosphonate drug regimen may further mediate the reduction of the inflammatory stimulus and prove beneficial in preventing or slowing osteophytes and cartilage degradation.…”

Transdermal Drug Delivery System of Aceclofenac for Rheumatoid Arthritis and the Effect of Permeation Enhancers: In vitro and in vivo Characterization

“…It acts as a potent inhibitor of Cyclooxygenase (COX) which in associated with the production of mediators of pain i.e., prostaglandins. Aceclofenac inhibits synthesis of the inflammatory cytokines interleukin (IL)-1 and tumor necrosis factor and prostaglandin E 2 (PGE2) production (FitzGerald and Patrono, 2001;Blot et al, 2000). It is associated with short half-life of about 2-3 h and gastro-intestinal side effects like gastrointestinal disturbances, peptic ulceration and gastrointestinal bleeding (Gupta et al, 2010;Grau et al, 1991;Semalty et al, 2010).…”

Aceclofenac in rheumatology: The golden mean

“…[24], ко-торые провели анализ биоптатов медиального надмыщелка бедра, взятых у 40 пациентов, страдавших выраженным или тяжелым гонартрозом. Проводилась инкубация хрящевой ткани с добавлением меченого глюкозамина в присутствии или отсутствии (контроль) ацеклофенака, мелоксикама и диклофенака.…”