Interleukin-1beta-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.
Publication Date: 2009-09-03 PubMed ID: 19723086DOI: 10.1111/j.1749-6632.2009.04687.xGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article examines the beneficial effect of curcumin (main polyphenol in turmeric) on osteoarthritis (OA) by inhibiting inflammation and degradation in the cartilage. The study uses an explant model to emulate the inflammation occurring in OA.
Experiment Design
- The study employs normal articular cartilage harvested from the joints of eight horses that were euthanized for non-research purposes. The harvested cartilages were used to create an explant model simulating the inflammatory events in OA.
- Initially, the cartilage explants were exposed to escalating concentrations of the proinflammatory cytokine, IL-1beta, to identify effective doses that would induce cartilage degeneration in the model.
- Upon establishing the effective doses, other cartilages were treated with IL-1beta at different concentrations (10 ng/mL or 25 ng/mL) and combined with various curcumin concentrations (0.1 micromol/L to 100 micromol/L).
Procedure and Results
- The cartilages were observed for 5 days, after which the amount of glycosaminoglycan (GAG) release from the explants was estimated using a colorimetric assay, dimethylmethylene blue.
- It was found that curcumin at a concentration of 100 micromol/L notably reduced the release of GAG stimulated by IL-1beta by an average of 20% at 10 ng/mL and 27% at 25 ng/mL, bringing it back to unstimulated control levels.
Conclusion and Implications
- The results highlight that the in-vitro explant model effectively simulates the inflammatory cytokine-mediated processes of cartilage destruction seen in OA.
- Clinically, it showcases the potential of curcumin in mitigating OA inflammation by inhibiting the inflammatory pathways and gene expression in cartilage cells (chondrocytes) stimulated with IL-1beta.
- This study suggests that exploiting natural remedies like curcumin can pave the way for effective countermeasures against OA.
Cite This Article
APA
Clutterbuck AL, Mobasheri A, Shakibaei M, Allaway D, Harris P.
(2009).
Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation.
Ann N Y Acad Sci, 1171, 428-435.
https://doi.org/10.1111/j.1749-6632.2009.04687.x Publication
Researcher Affiliations
- Division of Veterinary Medicine, School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, United Kingdom. Abigail.Clutterbuck@nottingham.ac.uk
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Cartilage / drug effects
- Cartilage / metabolism
- Cartilage / pathology
- Curcumin / pharmacology
- Dose-Response Relationship, Drug
- Extracellular Matrix / metabolism
- Glycosaminoglycans / metabolism
- Horses
- Insulin-Like Growth Factor I / pharmacology
- Interleukin-1beta / toxicity
- Metacarpophalangeal Joint / drug effects
- Metacarpophalangeal Joint / metabolism
- Metacarpophalangeal Joint / pathology
- Osteoarthritis / chemically induced
- Osteoarthritis / metabolism
- Osteoarthritis / prevention & control
- Tissue Culture Techniques
Grant Funding
- BBSRC/S/M/2006/13141 / Biotechnology and Biological Sciences Research Council
Citations
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