RESUMO
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.
Assuntos
Animais , Coelhos , Benzamidas/síntese química , Desdiferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Fenótipo , Pirimidinas/síntese química , Agrecanas/genética , Agrecanas/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzamidas/farmacologia , Sobrevivência Celular , Desdiferenciação Celular/imunologia , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Glicosaminoglicanos/análise , Imuno-Histoquímica , Citometria de Varredura a Laser , Cultura Primária de Células , Pirimidinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Engenharia TecidualRESUMO
Thiadiazoles are their derivatives exhibit a wide variety of pharmacological activities such as Antibacterial and anti-inflammatory. In the present study we have synthesized derivatives some 2,5 substituted 1,3,4-thiadiazoles. The structures of these synthesized compounds were confirmed by IR, NMR, and MASS spectra data. These compounds were evaluated for varies biological activities such as antibacterial and anti-inflammatory activity