目的研究核因子KB受体活化因子(receptor activator of NF-KB,RANK)及核因子KB受体活化因子配体(receptoractivator of NF-KB ligand,RANKL)和骨保护素(osteoprotegrin,OPG),在不同月龄雄性大鼠股骨表达的变化,探讨αD3对老龄大鼠RANK、...目的研究核因子KB受体活化因子(receptor activator of NF-KB,RANK)及核因子KB受体活化因子配体(receptoractivator of NF-KB ligand,RANKL)和骨保护素(osteoprotegrin,OPG),在不同月龄雄性大鼠股骨表达的变化,探讨αD3对老龄大鼠RANK、RANKL、OPG表达的影响。方法将6周龄、6月龄、24月龄、24月龄+αD3组Wistar大鼠分为甲、乙、丙、丁4组,每组15只。其中丁组为24月龄+αD3组,按0.05μg/kg/d-1灌胃,隔天1次,每周3次。连续10周。取左侧股骨远中干骺端1/2,采用RT-PCR测RANKL、RANK及OPG的mRNA的表达。取右侧股骨做免疫组化。结果与6周组相比,6月和24月组RANKLmRNA分别增加6.2倍和7.3倍,(P<0.05),OPGmRNA值随月龄逐步增加(P>0.05)。24月龄+αD3组较24月龄组RANK降低(P<0.05)、RANKL/OPG比值亦降低(P>0.05)。免疫组化结果显示RANKL、OPG表达于软骨和成骨细胞胞浆和胞核。24月龄+αD3干预组OPG表达较24月组增强。结论股骨RANKL/OPG值随月龄增加,有利于骨的吸收和转换;αD3有促进骨形成降低骨吸收的作用,其机制可能与降低RANK、RANKL/OPG比值有关。RANKL、OPG表达于同一类型的细胞,二者共同调节骨的代谢。展开更多
Background and aims: A substantial proportion of patients with inflammatory bo wel disease (IBD) develops osteopenia and osteoporosis in the course of disease. Recent data from a mouse model of colitis suggest that th...Background and aims: A substantial proportion of patients with inflammatory bo wel disease (IBD) develops osteopenia and osteoporosis in the course of disease. Recent data from a mouse model of colitis suggest that the receptor activator o f nuclear factor kappa B (RANKL)/osteoprotegerin (OPG) system may be responsible for bone loss. Methods: We investigated the activation state of the RANKL/OPG s ystem and its association with bone loss in human IBD. Plasma levels of OPG and RANKL were correlated with bone mineral density and current IBD therapy. Colonic secretion of OPG and RANKL and cell types responsible for such secretion were d etermined. Results:OPG plasma levels were elevated 2.4-fold in Crohn’s disease (CD) an- d 1.9-fold in ulcerative colitis (UC) whereas soluble RANKL (sRANKL) levels w ere not significantly different in IBD patients compared with healthy controls. High levels of OPG were released from colonic explant cultures (CEC) derived fro m inflamed IBD specimens, and colonic macrophages and dendritic cells costained for OPG. sRANKL levels from CEC were low both in IBD patients and healthy contro ls. Interestingly,increased expression of RANKL was mainly confined to cells in the lamina muscularis. A significant negative correlation was found between OPG plasma levels and femoral neck/lumbar spine bone mineral density. Conclusions: W e have demonstrated that IBD is associated with alterations in the RANKL/OPG sys tem. Applying results from a murine model of colitis associated bone loss, the c onstellation of OPG and sRANKL regulation observed in our study raises the possi bility that RANKL/OPG may contribute to the development of bone loss in IBD.展开更多
文摘目的研究核因子KB受体活化因子(receptor activator of NF-KB,RANK)及核因子KB受体活化因子配体(receptoractivator of NF-KB ligand,RANKL)和骨保护素(osteoprotegrin,OPG),在不同月龄雄性大鼠股骨表达的变化,探讨αD3对老龄大鼠RANK、RANKL、OPG表达的影响。方法将6周龄、6月龄、24月龄、24月龄+αD3组Wistar大鼠分为甲、乙、丙、丁4组,每组15只。其中丁组为24月龄+αD3组,按0.05μg/kg/d-1灌胃,隔天1次,每周3次。连续10周。取左侧股骨远中干骺端1/2,采用RT-PCR测RANKL、RANK及OPG的mRNA的表达。取右侧股骨做免疫组化。结果与6周组相比,6月和24月组RANKLmRNA分别增加6.2倍和7.3倍,(P<0.05),OPGmRNA值随月龄逐步增加(P>0.05)。24月龄+αD3组较24月龄组RANK降低(P<0.05)、RANKL/OPG比值亦降低(P>0.05)。免疫组化结果显示RANKL、OPG表达于软骨和成骨细胞胞浆和胞核。24月龄+αD3干预组OPG表达较24月组增强。结论股骨RANKL/OPG值随月龄增加,有利于骨的吸收和转换;αD3有促进骨形成降低骨吸收的作用,其机制可能与降低RANK、RANKL/OPG比值有关。RANKL、OPG表达于同一类型的细胞,二者共同调节骨的代谢。
文摘目的研究核因子κB受体活化因子配体(RANKL)/骨保护素(OPG)在多发性骨髓瘤(MM)中的表达情况。方法运用反转录聚合酶链反应(RT-PCR)检测人骨髓瘤细胞系(8226、XG1、XG7细胞)、患者MM细胞及MM患者骨髓基质细胞对RANKL/OPG的表达。结果 MM细胞系(8226、XG1、XG7细胞)及患者MM细胞均不表达RANKL及OPG m RNA;伴有骨病的MM患者骨髓基质细胞RANKL表达明显增加,OPG表达减低。结论 MM细胞不直接表达RANKL/OPG,可能通过调节RANKL/OPG的平衡间接参与MM骨病的发生。
文摘Background and aims: A substantial proportion of patients with inflammatory bo wel disease (IBD) develops osteopenia and osteoporosis in the course of disease. Recent data from a mouse model of colitis suggest that the receptor activator o f nuclear factor kappa B (RANKL)/osteoprotegerin (OPG) system may be responsible for bone loss. Methods: We investigated the activation state of the RANKL/OPG s ystem and its association with bone loss in human IBD. Plasma levels of OPG and RANKL were correlated with bone mineral density and current IBD therapy. Colonic secretion of OPG and RANKL and cell types responsible for such secretion were d etermined. Results:OPG plasma levels were elevated 2.4-fold in Crohn’s disease (CD) an- d 1.9-fold in ulcerative colitis (UC) whereas soluble RANKL (sRANKL) levels w ere not significantly different in IBD patients compared with healthy controls. High levels of OPG were released from colonic explant cultures (CEC) derived fro m inflamed IBD specimens, and colonic macrophages and dendritic cells costained for OPG. sRANKL levels from CEC were low both in IBD patients and healthy contro ls. Interestingly,increased expression of RANKL was mainly confined to cells in the lamina muscularis. A significant negative correlation was found between OPG plasma levels and femoral neck/lumbar spine bone mineral density. Conclusions: W e have demonstrated that IBD is associated with alterations in the RANKL/OPG sys tem. Applying results from a murine model of colitis associated bone loss, the c onstellation of OPG and sRANKL regulation observed in our study raises the possi bility that RANKL/OPG may contribute to the development of bone loss in IBD.
