RESUMO
OBJECTIVE: To explore the mechanism of Bushen Qiangji Granule (, BSQJ) in restraining the osteogenic differentiation of ankylosing spondylitis (AS) fifibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement and healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery as a control. Finite fifibroblast lines were established from these tissue samples to observe the effect of BSQJ on suppressing osteogenic differentiation of fifibroblasts. The expression of osteogenic marker gene corebinding factor a1 (Cbfa1) and Smad family proteins were examined by Western blot and real-time quantitative polymerase chain reaction (qPCR). RESULTS: The mRNA expression level of Cbfa1 was significantly higher in AS fibroblasts than that in normal fibroblasts and the expression of pSmad1, pSmad5, Smad4 and Cbfa1 in AS fibroblasts was also higher, demonstrating the activation of the BMP/Smads signal pathway in AS fifibroblasts. BSQJ-medicated serum not only restrained the mRNA and protein expression levels of Cbfa1 and inhibited protein expression level of Smad4 but also decreased the expression quantities of pSmad1 and pSmad5. CONCLUSIONS: BSQJ can inhibit osteogenic differentiation of AS fifibroblasts in vitro by suppressing the activation of the BMP/Smads signal pathway. This may be the important molecular mechanism of BSQJ in regulating AS ossifification.
Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/patologia , Osteogênese/efeitos dos fármacos , Soro/metabolismo , Proteínas Smad/metabolismo , Espondilite Anquilosante/patologia , Adulto , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Pessoa de Meia-Idade , Osteogênese/genética , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espondilite Anquilosante/genética , Adulto JovemRESUMO
OBJECTIVE: To explore the effects of Elemene, the essential oil of Curcuma wenyujin, on Bone morphogenetic protein/drosophila mothers against decapentaplegic proteins (BMP/SMADs) signal pathway in ankylosing spondylitis (AS) fibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement. Healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery were included as a control. Primary fibroblast cell lines were established from these tissue samples. Fibroblasts were incubated with Elemene for 48 hours. The protein expression was detected by Western blot. The mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). RESULTS: The results showed that the expression of proteins including SMAD1, pSMAD1, SMAD4 and Runt-related transcription factor 2 (RUNX2), and mRNA of RUNX2, which were over-expressed in AS fibroblasts were decreased in the AS fibroblasts cultured in medium with Elemene. CONCLUSIONS: Ele could have a hand in anti-osteogenic differentiation of AS fibroblasts by inhibiting the BMP/SMADs signal pathway and subsequently blocking expression of ossification marker genes RUNX2 that initiate the osteogenic differentiation.
Assuntos
Curcuma , Fibroblastos/metabolismo , Sesquiterpenos/farmacologia , Espondilite Anquilosante/metabolismo , Adulto , Artroplastia de Quadril , Proteínas Morfogenéticas Ósseas/biossíntese , Diferenciação Celular , Linhagem Celular , Subunidades alfa de Fatores de Ligação ao Core/biossíntese , Fibroblastos/efeitos dos fármacos , Articulação do Quadril/metabolismo , Humanos , Cápsula Articular/metabolismo , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/metabolismo , Osteoblastos/metabolismo , Óleos de Plantas/farmacologia , Transdução de Sinais , Proteínas Smad/biossíntese , Espondilite Anquilosante/cirurgia , Adulto JovemRESUMO
Molecular imaging enables noninvasive characterization, quantification and visualization of biological and pathological processes in vivo at cellular and molecular level. It plays an important role in drug discovery and development. The skillful use of molecular imaging can provide unique insights into disease processes, which greatly aid in identifications of target. Importantly, molecular imaging is widely applied in the pharmacodynamics study to provide earlier endpoints during the preclinical drug development process, since it can be applied to monitor the effects of treatment in vivo with the use of biomarkers. Herein, we reviewed the application of molecular imaging technologies in antitumor drug development process ranging from identification of targets to evaluation of therapeutic effect.