Curcumin mediated suppression of nuclear factor-kappaB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment
IntroductionOsteoarthritis (OA) and rheumatoid arthritis (RA) are characterised by joint inflammation and cartilage degradation. Although mesenchymal stem cell (MSC)-like progenitors are resident in the superficial zone of articular cartilage, damaged tissue does not possess the capacity for regeneration.
The high levels of pro-inflammatory cytokines present in OA/RA joints may impede the chondrogenic differentiation of these progenitors. Interleukin (IL)-1beta activates the transcription factor nuclear factor-kappaB (NF-kappaB), which in turn activates proteins involved in matrix degradation, inflammation and apoptosis.
Curcumin is a phytochemical capable of inhibiting IL-1beta-induced activation of NF-kappaB and expression of apoptotic and pro-inflammatory genes in chondrocytes. Therefore, the aim of the present study was to evaluate the influence of curcumin on IL-1beta-induced NF-kappaB signalling pathway in MSCs during chondrogenic differentiation.
Methods: MSCs were either cultured in a ratio of 1:1 with primary chondrocytes in high-density culture or cultured alone in monolayer with/without curcumin and/or IL-1beta.
Results: We demonstrate that although curcumin alone does not have chondrogenic effects on MSCs, it inhibits IL-1beta-induced activation of NF-kappaB, activation of caspase-3 and cyclooxygenase-2 in MSCs time and concentration dependently, as it does in chondrocytes.
In IL-1beta stimulated co-cultures, 4 hour pre-treatment with curcumin significantly enhanced the production of collagen type II, cartilage specific proteoglycans (CSPGs), beta1-integrin, as well as activating MAPKinase signaling and suppressing caspase-3 and cyclooxygenase-2.
Conclusions: Curcumin treatment may help establish a microenvironment in which the effects of pro-inflammatory cytokines are antagonized, thus facilitating chondrogenesis of MSC-like progenitor cells in vivo. This strategy may support the regeneration of articular cartilage.
Author: Constanze BuhrmannAli MobasheriUlrike MatisMehdi Shakibaei
Credits/Source: Arthritis Research &Therapy 2010, 12:R127
Published on: 2010-07-01
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