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
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
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 , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzamidas/farmacologia , Desdiferenciação Celular/imunologia , Sobrevivência Celular , 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 , Coelhos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Engenharia TecidualRESUMO
Although 75% of intussusceptions occur within the first two years of life, they can also develop in teenage years. This is a case report of a 13-year old boy with an ileocolorectal intussusception from a large caecal hamartoma (10 x 6 x 2 cm3) adjacent to the ileocaecal valve. Partial resection of the ascending colon and terminal ileum was performed, and the pathology of the resected mass revealed a hamartoma. Ileocolorectal intussusception secondary to hamartoma represents a particularly rare event in the paediatric population. With early surgical intervention, this patient's outcome was uneventful.
Assuntos
Doenças do Ceco/complicações , Hamartoma/complicações , Doenças do Íleo/etiologia , Intussuscepção/etiologia , Doenças Retais/etiologia , Adolescente , Doenças do Ceco/cirurgia , Hamartoma/cirurgia , Humanos , Doenças do Íleo/cirurgia , Valva Ileocecal , Intussuscepção/cirurgia , Masculino , Doenças Retais/cirurgiaRESUMO
Synoviocytes secrete "chondrocyte activating factors" (CAF) which, like recombinant interleukin-1 (IL-1), induce the synthesis of collagenase by cultures of articular chondrocytes. Enzyme synthesis is preceded by the appearance of collagenase mRNA some 3-5 hours after exposure of the chondrocytes to CAF or IL-1. Cycloheximide (CX) inhibits the appearance of this message in a dose-dependent manner. At a concentration of 5 micrograms/ml inhibition by CX is completely reversible, with superinduction being observed in certain experiments. Identification of the newly synthesised proteins which are required for collagenase mRNA induction would greatly advance our understanding of collagenase gene expression.