Interleukin‐1β–Induced Extracellular Matrix Degradation and Glycosaminoglycan Release Is Inhibited by Curcumin in an Explant Model of Cartilage Inflammation

Abstract

Osteoarthritis (OA) is a degenerative and inflammatory disease of synovial joints that is characterized by the loss of articular cartilage, for which there is increasing interest in natural remedies. Curcumin (diferuloylmethane) is the main polyphenol in the spice turmeric, derived from rhizomes of the plant Curcuma longa. Curcumin has potent chemopreventive properties and has been shown to inhibit nuclear factor kappaB-mediated inflammatory signaling in many cell types, including chondrocytes. In this study, normal articular cartilage was harvested from metacarpophalangeal and metatarsophalangeal joints of eight horses, euthanized for reasons other than research purposes, to establish an explant model mimicking the inflammatory events that occur in OA. Initially, cartilage explants (N= 8) were stimulated with increasing concentrations of the proinflammatory cytokine IL-1beta to select effective doses for inducing cartilage degeneration in the explant model. Separate cartilage explants were then cotreated with IL-1beta at either 10 ng/mL (n= 3) or 25 ng/mL (n= 3) and curcumin (0.1 micromol/L, 0.5 micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L). After 5 days, the percentage of glycosaminoglycan (GAG) release from the explants was assessed using a dimethylmethylene blue colorimetric assay. Curcumin (100 micromol/L) significantly reduced IL-1beta-stimulated GAG release in the explants by an average of 20% at 10 ng/mL and 27% at 25 ng/mL back to unstimulated control levels (P < 0.001). Our results suggest that this explant model effectively simulates the proinflammatory cytokine-mediated release of articular cartilage components seen in OA. Furthermore, the evidence suggests that the inflammatory cartilage explant model is useful for studying the effects of curcumin on inflammatory pathways and gene expression in IL-1beta-stimulated chondrocytes.

Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro

“…Treatment of OA with novel agents that can simultaneously target multiple cellular signaling pathways in chondrocytes will benefit from effectively downregulating inflammation without adverse systemic effects. We and others have shown that phytochemicals such as curcumin and resveratrol target the catabolic pathways mediated by the NF-jB signal transduction pathway in cartilage and might be used as clinically safe nutritional factors for the treatment of OA [13,15,26,34,36,47,50,54]. We have also shown that resveratrol and/or curcumin stimulate Sox-9 expression and inhibit the IL-1b-induced decreased Sox-9 expression that is necessary for the expression of cartilage matrix genes [15].…”

Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta‐analysis of randomized clinical trials

“…21 In vitro studies have also shown that curcuminoids inhibit IL-1b-induced glycosaminoglycan (GAG) release from animal and human OA cartilage explants. 22,23 Randomized clinical trials (RCTs) in animals have suggested that Curcuma extracts (comprised of mixtures of Indian and Javanese turmeric with essential oils) may have beneficial effects in treatment of OA 24 and results of a recent large observational study including 820 adults with painful OA showed evidence of benefits with curcuminoids in real-life clinical practice. 25 Several clinical trials investigating the effect of curcuminoids in OA have also been published.…”

The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses During Training

“…In another study, race records showed that less than 80% of the 2-year-old racehorses in training completed their training and went on to race [1]. Although the causes of lameness are varied, increased attention has been focused on the role of inflammatory mediators in this process [4][5][6]. Inflammation is associated with the production of proinflammatory cytokines, which are small hormone-like proteins produced in response to external stimuli.…”