Homocysteine attenuates the expression of osteocalcin but enhances osteopontin in MC3T3-E1 preosteoblastic cells
Homocysteine attenuates the expression of osteocalcin but enhances osteopontin in MC3T3-E1 preosteoblastic cells
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DOI：
10.1016/j.bbadis.2005.03.004
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发表时间：
2005-04-15
影响因子：
6.2
通讯作者：
Izumi, H
中科院分区：
文献类型：
--
作者：
Sakamoto, W;Isomura, H;Izumi, H
高半胱氨酸尿症是一种罕见的常染色体隐性遗传疾病，伴有早期全身性骨质疏松症，其特征是血浆中高半胱氨酸水平很高。然而，尚不清楚高同型半胱氨酸通过何种机制诱导骨质疏松症，尽管已知高同型半胱氨酸干扰胶原中交联的形成，这是骨形成的一个重要过程。因此，我们研究了同型半胱氨酸对MC 3 T3-E1前成骨细胞中骨钙素和骨桥蛋白表达的影响。使汇合细胞在含有10%胎牛血清（含或不含高半胱氨酸）的PPMI 1640中在37 ℃、95%加湿空气、5%CO2的气氛中生长。从细胞中分泌的骨钙素增加时间依赖性，直到培养结束（第34天）。但500 μ M同型半胱氨酸导致培养19天后骨钙素与对照相比降低约61%。另一方面，骨桥蛋白不被500 μ M同型半胱氨酸抑制，而是被激活，并且在从10天直到培养结束的时间段内范围为对照水平的134%-209%。从培养结束时骨钙素和骨桥蛋白mRNA的RT-PCR分析，与对照相比，100和500 μ M的同型半胱氨酸水平显著增加骨桥蛋白mRNA的表达（p < 0.05）。相反，骨桥蛋白mRNA的表达以剂量依赖性方式被抑制，显示了对骨桥蛋白mRNA的影响的镜像。这些研究结果表明，高同型半胱氨酸血症似乎是一个独立的风险因素，骨质疏松症的干扰成骨细胞的功能，（c）2005年爱思唯尔B. V.保留所有权利。
It has been pointed out that very high plasma levels of homocysteine are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. However, it is unclear by which mechanism hyperhomocysteine induces osteoporosis, although it is known to interfere eith the formation of cross-links in collagen, an essential process in bone formation. Therefore, we investigated the effect of homcysteine on expression of osteocalcin and osteopontin in MC3T3-E1 preosteoblastic cells. Confluent cells were grown in PPMI 1640 containing 10% fetal calf serum with or without homocysteine in an atmosphere of 95% humidified air, 5% CO2 at 37 degrees C. The secretion of osteocalcin from the cells increased time-dependently until the end of culture (day 34). but 500 mu M homocysteine led to an approximately 61% decrease for osteocalcin after 19 days of culture as compared with the control. On the other hand, osteopontin was not inhibited by 500 mu M homocysteine but rather activated, and ranged from 134%-209% of the control level in the period from 10 days until the end of culture. From analysis of RT-PCR for mRNA of osteocalcin and osteopontin at the end of the Culture, homocysteine levels of 100 and 500 mu M significantly increased the expression of osteopontin mRNA with the control (p < 0.05). In contrast, the expression of osteopontin mRNA was suppressed in a dose-dependent manner, showing a mirror image of the effect on osteopontin mRNA. These findings suggest that hyperhomocystenemia appears to be an independent risk factor for osteoporosis by disturbing osteoblast function, (c) 2005 Elsevier B.V. All rights reserved.