Mechanism of osteoblast differantiation by statins via stimulation of VEGF gene transcription
Mechanism of osteoblast differantiation by statins via stimulation of VEGF gene transcription
批准号:
15591976
负责人:
HORIUCHI Noboru
金额:
$2.37万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2003
资助国家:
日本
项目状态:
已结题
起止时间:
2003 至 2004
中文摘要
他汀类药物,如辛伐他汀,可抑制胆固醇合成。我们研究了他汀类药物对成骨细胞血管内皮生长因子(VEGF)表达的影响。辛伐他汀(10^<;-6>;M)可时间依赖性地增强MC3T3-E1细胞中血管内皮生长因子的表达。辛伐他汀显著增加了血管内皮生长因子启动子-荧光素酶的转录激活。结果表明,辛伐他汀对血管内皮生长因子基因的刺激在本质上是转录的。他汀类药物通过减少蛋白预烯基化和P13K途径刺激成骨细胞表达血管内皮生长因子,促进成骨细胞分化。观察阿托伐他汀对去卵巢(OVX)大鼠骨密度的影响。联合应用阿托伐他汀(2 mg/kg)和17β-雌二醇(E_2)后,腰椎(L2-L4)骨密度明显高于单独应用E_2或阿托伐他汀。同时注射阿托伐他汀(2 mg/kg)和hPTH(1-34),小剂量(1rig/kg)可显著提高去势大鼠腰椎骨密度。这些结果表明,长期服用阿托伐他汀似乎适度提高了次最大剂量E_2和hPTH(1-34)治疗的OVX大鼠的腰椎骨密度。
英文摘要
Statins such as simvastatin inhibit cholesterol synthesis. We investigated statin effects on vascular endothelial growth factor (VEGF) expression in osteoblastic cells. Simvastatin (10^<-6> M) time-dependently augmented VEGF mRNA expression in MC3T3-E1 cells. Transcriptional activation of a VEGF promoter - luciferase construct significantly increased by simvastatin administration. The results indicate that the stimulation of the VEGF gene by simvastatin is transcriptional in nature. Statins stimulate VEGF expression in osteoblasts via reduced protein prenylation and the P13K pathway, promoting osteoblastic differentiation. We investigated the in vivo effect of atorvastatin on bone mineral density (BMD) in ovariectomized (OVX) rats. The combination of atorvastatin (2 mg/kg) and 17β-estradiol (E_2) significantly enhanced the BMD of lumbar vertebrae (L2-L4) compared to that of either E_2 or atorvastatin alone. Concomitant injections of atorvastatin (2 mg/kg) with hPTH(1-34) at a low dose (1 rig/kg) significantly enhanced the BMD of lumbar vertebrae in OVX rats. These findings demonstrate that chronic administration of atorvastatin appears to modestly enhance the BMD of the lumbar vertebrae of OVX rats treated with submaximal doses of E_2 and hPTH( 1-34).
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Tetsuya Kawane: "Parathyroid hormone (PTH) down-regulates PTH/PTH-related protein receptor gene expression in UMR-106 osteoblast-like cells via a 3',5'-cyclic adenosine monophosphate-dependent, protein kinase A-independent pathway."Journal of Endocrinolog
Tetsuya Kawane:“甲状旁腺激素 (PTH) 通过 3,5-环单磷酸腺苷依赖性、蛋白激酶 A 依赖性途径下调 UMR-106 成骨细胞样细胞中 PTH/PTH 相关蛋白受体基因的表达。
DOI:
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发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
DOI:
10.1210/en.2003-1010
发表时间:
2004-03-01
期刊:
ENDOCRINOLOGY
影响因子:
4.8
作者:
[Matsunuma, A, Kawane, T, Horiuchi, N]
通讯作者:
Horiuchi, N
Leptin corrects increased gene expression of renal 25-hydroxyvitamin D_3- lα-hydroxylase and -24-hydroxylase in leptin- deficient, ob/ob mice.
瘦素可纠正瘦素缺乏的 ob/ob 小鼠中肾脏 25-羟基维生素 D_3-1α-羟化酶和 -24-羟化酶基因表达的增加。
DOI:
--
发表时间:
2004
期刊:
Endocrinology 145-3
影响因子:
--
作者:
[Ayako Matsunuma, Tetsuya Kawane, Toyonobu Maeda, Setsuo Hamada, Noboru Horiuchi]
通讯作者:
Noboru Horiuchi
Effect of leptin on renal 1α-hydroxylase expression in mice.
瘦素对小鼠肾1α-羟化酶表达的影响。
DOI:
--
发表时间:
2004
期刊:
Proceedings of 12th International Congress of Endocrinology.
影响因子:
--
作者:
[Hamaguchi, H., Fujimoto, K., Kawamoto, T., Noshiro, M., Maemura, K., Takeda, N., Nagai, R., Furukawa, M., Honma, S., Honma, K., Kurihara, H., Kato, Y, Noboru Horiuchi]
通讯作者:
Noboru Horiuchi
Suppression of parathyroid hormone-related protein expression by all trans-retinoic acid in human oral squamous carcinoma cells (HSC-3).
全反式视黄酸抑制人口腔鳞状细胞癌细胞 (HSC-3) 中甲状旁腺激素相关蛋白的表达。
DOI:
--
发表时间:
2004
期刊:
Journal of Oral Biosciences 46-6
影响因子:
--
作者:
[Masatoshi Abe, Nobutaka Haramoto, Hidefumi Itoh, Noboru Horiuchi.]
通讯作者:
Noboru Horiuchi.
共 18 条
Elucidation of Regulatory Mechanisms of Osteoblastic and Chondrocytic Differentiation by Statins
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批准号:18592045
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.49万
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财政年份:2006
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负责人:HORIUCHI Noboru
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依托单位:
Disorder of vitamin D metabolism in steroid-induced osteoporosis
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批准号:10470393
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项目类别:Grant-in-Aid for Scientific Research (B).
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资助金额:$8.45万
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财政年份:1998
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负责人:HORIUCHI Noboru
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依托单位:
Parathyroid hormone-related protein mRNA expression and oral cancer progression
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批准号:05557081
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项目类别:Grant-in-Aid for Developmental Scientific Research (B)
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资助金额:$6.72万
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财政年份:1993
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负责人:HORIUCHI Noboru
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依托单位:
海外基金