Using tissue engineering technique to repair cartilage damage caused by osteoarthritis is a promising strategy. However, the regenerated tissue usually is fibrous cartilage, which has poor mechanical characteristics compared to hyaline cartilage. Chondrocyte hypertrophy plays an important role in this process. Thus, it is very important to find out a suitable way to maintain the phenotype of chondrocytes and inhibit chondrocyte hypertrophy. Curcumin deriving from turmeric was reported with anti-inflammatory and antitumor pharmacological effects. However, the role of curcumin in metabolism of chondrocytes, especially in the chondrocyte hypertrophy remains unclear. Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering as seed cells. So we investigated the effect of curcumin on chondrogenesis and chondrocyte hypertrophy in MSCs through examination of cell viability, glycosaminoglycan synthesis and specific gene expression. We found curcumin had no effect on expression of chondrogenic markers including Sox9 and Col2a1 while hypertrophic markers including Runx2 and Col10a1 were down-regulated. Further exploration showed that curcumin inhibited chondrocyte hypertrophy through Indian hedgehog homolog (IHH) and Notch signalings. Our results indicated curcumin was a potential agent in modulating cartilage homeostasis and maintaining chondrocyte phenotype.Key words curcumin; mesenchymal stem cell; chondrocyte hypertrophy; Indian hedgehog homolog; neurogenic locus notch homolog Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and disability.1) Seventy percent of the population older than 65 years is suffering from varying degrees of OA.2)The pathogenesis of cartilage injury caused by OA is the disruption of the homeostasis between catabolism and anabolism of extracellular matrix.3) However, limited by the intrinsic regeneration capacity of cartilage tissue, repairing damaged articular cartilage currently is a significant challenge. 4,5) With the advances in materials science, cell biology, biomechanics, using tissue engineering technology to construct cartilage provides a novel method for repairing damaged cartilage.6) Mesenchymal stem cells (MSCs) have potential of differentiation into chondrocytes and have got the priority in the seed cells choosing list because of their traits in rich resources, easy to get and low immunogenicity. 7,8) However, the regenerated tissue-engineered cartilage usually is fibrous cartilage rather than hyaline cartilage.9) The chondrocytes in fibrous cartilage proceed in hypertrophic differentiation and secret Col10a1 and matrix metalloproteinase 13 (Mmp13).10) Therefore, suppressing chondrocyte hypertrophy is the key issue to build a stable hyaline cartilage.Curcumin is effective substance of turmeric and possesses various pharmacological effects, including antioxidant, anti-bacterial, anti-tumor and anti-inflammatory.11-13) A recent study has reported that curcumin may be a potential therapeutic candidate for Helicobacter pylori associated diseas...