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
Background/Aims: There is increasing interest in the influence of excess body weight and associated metabolic factors on the liver. In patients with non-alcoholic steatohepatitis, lower levels of adiponectin were asso...Background/Aims: There is increasing interest in the influence of excess body weight and associated metabolic factors on the liver. In patients with non-alcoholic steatohepatitis, lower levels of adiponectin were associated with higher g rades of hepatic steatosis and necroinflammatory activity, suggesting a pathophysiological role for this adipokine in liver disease. Methods: We studied 194 consecutive patients with untreated chronic HCV, t o assess the relationship between adiponectin and its receptors and hepatic stea tosis, fibrosis and inflammation. Results: Significant negative correlations bet ween serum adiponectin and male gender, body mass index and serum insulin were o bserved. However, there was no association between serum adiponectin and stage o f fibrosis and lower levels of serum adiponectin were associated with the presen ce of steatosis in males only. In contrast, there was a significant increase in serum adiponectin and hepatic adiponectin immunoreactivity with increasing infla mmation. The hepatic mRNA expression of the adiponectin receptors, AdipoR1 and A dipoR2, displayed significant but opposite associations with phosphoenolpyruvate carboxykinase (PEPCK) gene expression, a substitute marker of hepatic insulin s ensitivity. Conclusions: In patients with chronic HCV, adiponectin was associate d with steatosis only in males and was paradoxically increased with inflammation . Our results suggest that the role of adiponectin in chronic liver diseases may be linked to gender and etiology.展开更多
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.
文摘Background/Aims: There is increasing interest in the influence of excess body weight and associated metabolic factors on the liver. In patients with non-alcoholic steatohepatitis, lower levels of adiponectin were associated with higher g rades of hepatic steatosis and necroinflammatory activity, suggesting a pathophysiological role for this adipokine in liver disease. Methods: We studied 194 consecutive patients with untreated chronic HCV, t o assess the relationship between adiponectin and its receptors and hepatic stea tosis, fibrosis and inflammation. Results: Significant negative correlations bet ween serum adiponectin and male gender, body mass index and serum insulin were o bserved. However, there was no association between serum adiponectin and stage o f fibrosis and lower levels of serum adiponectin were associated with the presen ce of steatosis in males only. In contrast, there was a significant increase in serum adiponectin and hepatic adiponectin immunoreactivity with increasing infla mmation. The hepatic mRNA expression of the adiponectin receptors, AdipoR1 and A dipoR2, displayed significant but opposite associations with phosphoenolpyruvate carboxykinase (PEPCK) gene expression, a substitute marker of hepatic insulin s ensitivity. Conclusions: In patients with chronic HCV, adiponectin was associate d with steatosis only in males and was paradoxically increased with inflammation . Our results suggest that the role of adiponectin in chronic liver diseases may be linked to gender and etiology.
