Curcumin mediated suppression of nuclear factor-KB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment

Introduction: Osteoarthritis (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)-1 beta activates the transcription factor nuclear factor-KB
(NF-KB), which in turn activates proteins involved in matrix
degradation, inflammation and apoptosis. Curcumin is a
phytochemical capable of inhibiting IL-1 beta-induced activation of
NF-KB 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-1 beta-induced NF-KB
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-1 beta. Results: We demonstrate
that although curcumin alone does not have chondrogenic effects on
MSCs, it inhibits IL-1 beta-induced activation of NF-KB, activation
of caspase-3 and cyclooxygenase-2 in MSCs time and concentration
dependently, as it does in chondrocytes. In IL-1 beta stimulated
co-cultures, four-hour pre-treatment with curcumin significantly
enhanced the production of collagen type II, cartilage specific
proteoglycans (CSPGs), beta 1-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.