脂联素调控人成骨细胞OPG／RANKL表达的信号转导机制  

Signal pathway involved in the effects of adiponectin on OPG and RANKL expressions in human osteoblasts

作　　者：刘幼硕[1] 罗湘杭[2] 袁凌青[2] 谢辉[2] 詹俊鲲[1] 廖二元[1] 

机构地区：[1]中南大学湘雅二医院老年医学科,长沙410011 [2]中南大学湘雅二医院代谢内分泌研究所

出　　处：《中华内分泌代谢杂志》2008年第4期364-367,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助项目（30572078）

摘　　要：目的研究脂联素调控人成骨细胞护骨素（OPG）和NF-κB受体活化因子配体（RANKL）表达的作用机制。方法人成骨细胞OPG和RANKLmRNA的表达以实时PCR检测，p38丝裂原活化蛋白激酶（p38MAPK）、细胞外信号调节激酶（ERK1／2）、c-Jun氨基端激酶（JNK）的磷酸化水平用Western印迹法检测。应用小分子RNA干扰技术（siRNA）阻断脂联素受体（AdR）表达，并以p38MAPK抑制剂（SB203580）和JNK抑制剂（SP600125）干预，以观察脂联素对人成骨细胞OPG／RANKL作用的调节机制。结果用siRNA沉默AdR1的表达可消除脂联素促进人成骨细胞RANKL表达和抑制OPG表达的作用；脂联素干预前予SB203580阻断p38MAPK后，也可消除脂联素对成骨细胞RANKL和OPG的作用，而SP600125并无作用。结论在人成骨细胞中，脂联素通过AdR1／p38MARK途径促进RANKL表达和抑制OPG的表达。Objective To investigate the mechanisms of action of adiponectin on receptor activator of NF-κB ligand （RANKL） and osteoprotegerin （OPG） expressions in human osteoblasts. Methods Real-time PCR was used to detect the expressions of RANKL and OPG mRNA in cultured human osteoblasts. The phosphorylations of JNK, p38 mitogen-activated protein kinase （MAPK） , ERK1/2 were assayed by Western blot. RNA interference for adiponectin receptor, MAPK inhibitors SB203580 and SP600125 were used for elucidating the mechanism of the action of adiponectin in regulating OPG and RANKL expressions. Results Suppression of adiponectin receptor-1 （AdR1） expression with siRNA abolished the adiponectin-regulated expressions of OPG and RANKL mRNA in human osteoblasts. Furthermore, pretreatment of osteoblasts with MAPK inhibitor SB203580 abolished the expressions of adiponectin-regulated RANKL and OPG mRNA, but SP600125 did not show the effect. Conclusion Adiponectin induces the expression of RANKL and inhibits the expression of OPG in human osteoblasts through AdR1/p38 MAPK pathways.

关 键 词：脂联素 成骨细胞 护骨素 NF-κB受体活化因子配体 丝裂原活化蛋白激酶 骨质疏松 

分 类 号：R580[医药卫生—内分泌]