Effect of JJYMD-C, a novel synthetic derivative of gallic acid, on proliferation and phenotype maintenance in rabbit articular chondrocytes in vitro

Abstract

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.

Inhibition of protein kinase R protects against palmitic acid–induced inflammation, oxidative stress, and apoptosis through the JNK/NF‐kB/NLRP3 pathway in cultured H9C2 cardiomyocytes

“…Subsequently, the cells were rinsed in PBS. They were then examined and photographed using an inverted phase‐contrast microscope (Zeiss Corporation) …”

Synthesis, Biological Evaluation, and Docking Studies of a Novel Sulfonamido-Based Gallate as Pro-Chondrogenic Agent for the Treatment of Cartilage

“…However, it exhibited an inhibitive effect on chondrocytes growth in the concentration between 0 and 40 μg/mL in a cytotoxicity assay, and therefore the subsequent experiments were not performed in this way. Nevertheless, other synthesized sulfonamido-based gallate analogues we had investigated previously [ 26 , 27 , 28 , 29 , 30 ] presented great effect on promoting chondrocyte growth and upregulating the expression of aggrecan, collagen II and Sox9, which confirm the fact that coupling of the phenyl ring with the sulfonamide group is critical for the pro-chondrogenic activity of these compounds and this docking model would provide us with a quick method to screen out the effective compounds. More docking studies should be performed in our further investigation to optimize their structures.…”

“…Recently, we have reported a series of synthesized sulfonamido-based gallates and their effectiveness on chondro-protection [ 26 , 27 , 28 , 29 , 30 ], which confirm the fact that coupling of the phenyl ring with the sulfonamide group is critical for the activity of preventing cartilage degeneration. Herein, another analog was synthesized and shown to be effective in biological evaluation, a docking study was therefore performed to provide an explanation for its activity and selectivity.…”

Chondro-Protective and Antiarthritic Effects of Sulfonamido-Based Gallate–ZXHA-TC in Vitro and in Vivo

“…However, GA has a much weaker effect than ZXHA-TC. We previously demonstrated that GA derivatives have stronger antioxidant effects than GA − , possibly because GA is much more hydrophilic and cytotoxic than its esters. In an in vivo study, we also observed that ZXHA-TC blocks ROS production (Figure C).…”