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Braz. j. med. biol. res ; 47(8): 637-645, 08/2014. tab, graf
Article in English | LILACS | ID: lil-716279

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.


Subject(s)
Animals , Rabbits , Benzamides/chemical synthesis , Cell Dedifferentiation/drug effects , Cell Proliferation/drug effects , Chondrocytes/drug effects , Phenotype , Pyrimidines/chemical synthesis , Aggrecans/genetics , Aggrecans/metabolism , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Benzamides/pharmacology , Cell Survival , Cell Dedifferentiation/immunology , Chondrocytes/cytology , Chondrocytes/metabolism , Chondrogenesis/drug effects , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type II/genetics , Collagen Type II/metabolism , Glycosaminoglycans/analysis , Immunohistochemistry , Laser Scanning Cytometry , Primary Cell Culture , Pyrimidines/pharmacology , Real-Time Polymerase Chain Reaction , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Tissue Engineering
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