Xu G J, Lu Z H, Lin X, Lin C W, Zheng L, Zhao J M
The First Affiliated Hospital, Osteopathy Ward, Guangxi Medical University, Nanning, Guangxi, China.
The Medical and Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, China.
Braz J Med Biol Res. 2014 Aug;47(8):637-45. doi: 10.1590/1414-431x20143935. Epub 2014 Jul 8.
Tissue engineering encapsulated cells such as chondrocytes in the carrier matrix have been widely used to repair cartilage defects. However, chondrocyte phenotype is easily lost when chondrocytes are expanded in vitro by a process defined as "dedifferentiation". To ensure successful therapy, an effective pro-chondrogenic agent is necessary to overcome the obstacle of limited cell numbers in the restoration process, and dedifferentiation is a prerequisite. Gallic acid (GA) has been used in the treatment of arthritis, but its biocompatibility is inferior to that of other compounds. In this study, we modified GA by incorporating sulfamonomethoxine sodium and synthesized a sulfonamido-based gallate, JJYMD-C, and evaluated its effect on chondrocyte metabolism. Our results showed that JJYMD-C could effectively increase the levels of the collagen II, Sox9, and aggrecan genes, promote chondrocyte growth, and enhance secretion and synthesis of cartilage extracellular matrix. On the other hand, expression of the collagen I gene was effectively down-regulated, demonstrating inhibition of chondrocyte dedifferentiation by JJYMD-C. Hypertrophy, as a characteristic of chondrocyte ossification, was undetectable in the JJYMD-C groups. We used JJYMD-C at doses of 0.125, 0.25, and 0.5 µg/mL, and the strongest response was observed with 0.25 µg/mL. This study provides a basis for further studies on a novel agent in the treatment of articular cartilage defects.
组织工程将软骨细胞等细胞包裹在载体基质中，已被广泛用于修复软骨缺损。然而，当软骨细胞在体外通过一种被定义为“去分化”的过程进行扩增时，软骨细胞表型很容易丧失。为确保治疗成功，一种有效的促软骨生成剂对于克服修复过程中细胞数量有限的障碍是必要的，而去分化是一个先决条件。没食子酸（GA）已被用于治疗关节炎，但其生物相容性不如其他化合物。在本研究中，我们通过加入磺胺间甲氧嘧啶钠对GA进行修饰，合成了一种基于磺酰胺的没食子酸盐JJYMD-C，并评估了其对软骨细胞代谢的影响。我们的结果表明，JJYMD-C能有效提高Ⅱ型胶原、Sox9和聚集蛋白聚糖基因的水平，促进软骨细胞生长，并增强软骨细胞外基质的分泌和合成。另一方面，Ⅰ型胶原基因的表达被有效下调，表明JJYMD-C对软骨细胞去分化有抑制作用。在JJYMD-C组中未检测到作为软骨细胞骨化特征的肥大现象。我们使用了0.125、0.25和0.5μg/mL剂量的JJYMD-C，在0.25μg/mL时观察到最强反应。本研究为进一步研究一种治疗关节软骨缺损的新型药物提供了依据。
