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

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-1β.We 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.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.Osteoarthritis (OA) and rheumatoid arthritis (RA) involve degenerative changes in the joint, leading to loss of function, pain and significant disability [1]. OA and RA are not only common joint diseases in the elderly population but increasingly they affect young individuals. Collectively, they represent a large proportion of orthopaedic cases [2]. Articular cartilage is an avascular, alymphatic and aneural tissue with bradytrophic characteristics and a very poor capacity for self-repair and regeneration [3]. Cartilage repair is ineffective and often leads to replacement of the articular cartilage by a mechanically inferior fibrocartilage tissue thus promoting progressive degeneration and impairment of joint function [4]. This inherent weakness in cartilage repair highlights the acute need for novel treatments using tissue engineering and regenerative medicine, and innovative new regenerative strategies that involve stimulation of articular cartilage repair in vivo.OA is characterized by an imbalance between cartilage anabolism and cat