Cao Zhen, Dou Ce, Dong Shiwu
Department of Anatomy, Third Military Medical University.
Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University.
Chem Pharm Bull (Tokyo). 2017;65(8):762-767. doi: 10.1248/cpb.c17-00225.
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 anti-tumor 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.
利用组织工程技术修复骨关节炎引起的软骨损伤是一种很有前景的策略。然而,再生组织通常是纤维软骨,与透明软骨相比,其力学特性较差。软骨细胞肥大在这一过程中起重要作用。因此,找到一种合适的方法来维持软骨细胞的表型并抑制软骨细胞肥大非常重要。姜黄素来源于姜黄,据报道具有抗炎和抗肿瘤药理作用。然而,姜黄素在软骨细胞代谢中的作用,尤其是在软骨细胞肥大方面仍不清楚。间充质干细胞(MSCs)作为种子细胞被广泛应用于软骨组织工程。因此,我们通过检测细胞活力、糖胺聚糖合成和特定基因表达,研究了姜黄素对MSCs软骨生成和软骨细胞肥大的影响。我们发现姜黄素对包括Sox9和Col2a1在内的软骨生成标志物的表达没有影响,而包括Runx2和Col10a1在内的肥大标志物的表达则下调。进一步的探索表明,姜黄素通过印度刺猬同源物(IHH)和Notch信号通路抑制软骨细胞肥大。我们的结果表明,姜黄素是调节软骨内环境稳定和维持软骨细胞表型的潜在药物。