RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells.
RANKL is a downstream mediator for insulin-induced osteoblastic differentiation of vascular smooth muscle cells.
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RANKL 是胰岛素诱导血管平滑肌细胞成骨细胞分化的下游介质
DOI：
10.1371/journal.pone.0029037
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Liao EY
中科院分区：
文献类型：
--
作者：
Yuan LQ;Zhu JH;Wang HW;Liang QH;Xie H;Wu XP;Zhou H;Cui RR;Sheng ZF;Zhou HD;Zhu X;Liu GY;Liu YS;Liao EY
已有研究表明循环中胰岛素水平与动脉钙化呈正相关，但胰岛素与动脉钙化的关系仍存在争议，其机制尚不清楚。我们使用钙化血管平滑肌细胞（CVSMCs），一个特殊的血管平滑肌细胞亚群，可以自发表达成骨细胞表型基因和形成钙化结节，研究胰岛素对CVSMCs的成骨分化的影响和涉及的细胞信号。我们的实验表明，胰岛素可以促进碱性磷酸酶（ALP）活性，骨钙素的表达和矿化结节的形成在CVSMC。用小干扰RNA（siRNA）抑制核因子κB受体激活因子配体（RANKL）可消除胰岛素诱导的ALP活性。胰岛素诱导细胞外信号调节激酶（ERK）1/2、丝裂原活化蛋白激酶（MAPK）和RAC-α丝氨酸/苏氨酸蛋白激酶（Akt）的活化。此外，ERK 1/2抑制剂PD 98059预处理人成骨细胞，而不是磷酸肌醇3-激酶（PI 3 K）抑制剂LY 294002或Akt抑制剂1 L-6-羟甲基-手性-肌醇2-（R）-2-O-甲基-3-O-十八烷基碳酸酯（HIMO），取消了胰岛素诱导的RANKL分泌，并阻断了胰岛素对CVSMC ALP活性的促进作用。重组RANKL蛋白可恢复RANKL siRNA降低的胰岛素刺激的CVSMCs ALP活性。这些数据表明，胰岛素可通过ERK 1/2激活而非PI 3 K/Akt激活增加RANKL表达来促进CVSMC的成骨分化。
Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation.
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DOI：
10.2215/cjn.00010108
发表时间：
2008-09-01
影响因子：
9.8
作者：
Kobayashi, Shuzo;Oka, Machiko;Ohtake, Takayasu
通讯作者：
Ohtake, Takayasu
影响因子：
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作者：
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影响因子：
3.7
作者：
Shan PF;Lu Y;Cui RR;Jiang Y;Yuan LQ;Liao EY
通讯作者：
Liao EY
影响因子：
16.2
作者：
Snell-Bergeon, JK;Hokanson, JK;Rewers, M
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Rewers, M
脂联素缺陷小鼠动脉钙化的发展：脂联素调节动脉钙化
影响因子：
6.2
作者：
Luo, Xiang-Hang;Zhao, Li-Ling;Liao, Er-Yuan
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Liao, Er-Yuan