In vitro effect of a synthesized sulfonamido-based gallate on articular chondrocyte metabolism.
Autologous chondrocyte implantation (ACI) is a promising strategy for cartilage repair and reconstitution. However, limited cell numbers and the dedifferentiation of chondrocytes present major difficulties to the success of ACI therapy. Therefore, it is important to find effective pro-chondrogenic agents that restore these defects to ensure a successful therapy. In this study, we synthesized a sulfonamido-based gallate, namely N-[4-(4,6-dimethyl-pyrimidin-2-ylsulfamoyl)-phenyl]-3,4,5-trihydroxy-benzamide (EJTC), and investigated its effects on rabbit articular chondrocytes through an examination of its specific effects on cell proliferation, morphology, viability, GAG synthesis, and cartilage-specific gene expression. The results show that EJTC can effectively promote chondrocyte growth and enhance the secretion and synthesis of cartilage ECM by upregulating the expression levels of the aggrecan, collagen II, and Sox9 genes. The expression of the collagen I gene was effectively downregulated, which indicates that EJTC inhibits chondrocytes dedifferentiation. Chondrocyte hypertrophy, which may lead to chondrocyte ossification, was also undetectable in the EJTC-treated groups. The recommended dose of EJTC ranges from 3.125 μg/mL to 7.8125 μg/mL, and the most profound response was observed with 7.8125 μg/mL. This study may provide a basis for the development of a novel agent for the treatment of articular cartilage defects.
School of Chemistry and Chemical Engineering, Guangxi University, 100 Daxue Dong Road, Nanning, Guangxi 530004, China; Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China.
Xiao
X
Lin
The Medical and Scientific Research Center, Guangxi Medical University, Nanning 530021, China; Research Center for Regenerative Medicine, Guangxi Medical University, Nanning 530021, China.
Li
L
Zheng
The Medical and Scientific Research Center, Guangxi Medical University, Nanning 530021, China.
Qin
Q
Liu
Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China.
Buming
B
Liu
School of Chemistry and Chemical Engineering, Guangxi University, 100 Daxue Dong Road, Nanning, Guangxi 530004, China.
Bingli
B
Jiang
School of Chemistry and Chemical Engineering, Guangxi University, 100 Daxue Dong Road, Nanning, Guangxi 530004, China.
Xiaoyu
X
Peng
School of Chemistry and Chemical Engineering, Guangxi University, 100 Daxue Dong Road, Nanning, Guangxi 530004, China. Electronic address: cuiwulin@163.com.
Cuiwu
C
Lin
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C000593990:N-(4-(4,6-dimethylpyrimidin-2-ylsulfamoyl)phenyl)-3,4,5-trihydroxybenzamide; D013449:Sulfonamides; D005707:Gallic Acid
Chondrocyte; Dedifferentiation; Gallic acid; Pro-chondrogenic agent; Rabbit articular cartilage; Sulfadimidine