Curcumin mediated suppression of nuclear factor-κB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironmentReport as inadecuate




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Arthritis Research and Therapy

, 12:R127

First Online: 01 July 2010Received: 03 February 2010Revised: 14 May 2010Accepted: 01 July 2010

Abstract

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-1β activates the transcription factor nuclear factor-κB NF-κB, which in turn activates proteins involved in matrix degradation, inflammation and apoptosis. Curcumin is a phytochemical capable of inhibiting IL-1β-induced activation of NF-κB 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-1β-induced NF-κB signalling pathway in MSCs during chondrogenic differentiation.

MethodsMSCs 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-1β.

ResultsWe demonstrate that although curcumin alone does not have chondrogenic effects on MSCs, it inhibits IL-1β-induced activation of NF-κB, activation of caspase-3 and cyclooxygenase-2 in MSCs time and concentration dependently, as it does in chondrocytes. In IL-1β stimulated co-cultures, four-hour pre-treatment with curcumin significantly enhanced the production of collagen type II, cartilage specific proteoglycans CSPGs, β1-integrin, as well as activating MAPKinase signaling and suppressing caspase-3 and cyclooxygenase-2.

ConclusionsCurcumin 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.

AbbreviationsAP303aalkaline phosphatase linked sheep anti-mouse

AP304Asheep anti-rabbit secondary antibodies

DMSOdimethylsulfoxide

COX-2cyclooxygenase-2

CSPGcartilage specific proteoglycans

ECMextracellular matrix

ERK 1-2extracellular regulated kinases 1 and 2

FCSfetal calf serum

IKKIκB kinase

ILinterleukin

MAB1965anti-β1-integrin antibody

MAB2015monoclonal anti-adult cartilage-specific proteoglycan antibody

MAPKmitogen-activated protein kinase

MMPmatrix metalloproteinase

MSCmesenchymal stem cell

MTT3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide

NFnuclear factor

NF-κBnuclear factor-κB

OAosteoarthritis

PAB746polyclonal anti-collagen type II antibody

PARPpolyADP-Ribose polymerase

PBSphosphate buffered saline

RArheumatoid arthritis

Shcsrc homology collagen

TNFtumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3065 contains supplementary material, which is available to authorized users.

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Author: Constanze Buhrmann - Ali Mobasheri - Ulrike Matis - Mehdi Shakibaei

Source: https://link.springer.com/



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