Plasminogen activator inhibitor-1 is involved in streptozotocin-induced bone loss in female mice.
Plasminogen activator inhibitor-1 is involved in streptozotocin-induced bone loss in female mice.
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作者：
Tamura Y;Kawao N;Okada K;Yano M;Okumoto K;Matsuo O;Kaji H
在糖尿病患者中，由于骨形成受损，骨折的风险很高。然而，糖尿病性骨质疏松症发生发展的机制细节仍不清楚。在本研究中，我们研究了纤溶酶原激活物抑制剂（派）-1在1型糖尿病骨质疏松症的发病机制中的作用，通过使用派-1缺陷小鼠。定量计算机断层扫描分析表明，派-1缺乏保护对链脲佐菌素诱导的雌性小鼠骨丢失，但在雄性小鼠中没有。派-1缺乏钝化的Runx 2，osterix，和胫骨碱性磷酸酶的水平的变化，以及血清骨钙素水平的糖尿病状态抑制的雌性小鼠。此外，雌性小鼠胫骨中的破骨细胞水平在糖尿病中受到抑制，也因派-1缺乏而减弱。链脲佐菌素仅使雌性小鼠肝脏派-1 mRNA水平显著升高。体外研究表明，用活性派-1处理抑制雌性小鼠颅骨的原代成骨细胞中成骨基因和矿化的水平。总之，目前的研究表明派-1参与了女性1型糖尿病骨质疏松症的发病机制。派-1在肝脏中的表达和骨细胞对派-1的敏感性可能是其机制之一。
In diabetic patients, the risk of fracture is high because of impaired bone formation. However, the details of the mechanisms in the development of diabetic osteoporosis remain unclear. In the current study, we investigated the role of plasminogen activator inhibitor (PAI)-1 in the pathogenesis of type 1 diabetic osteoporosis by using PAI-1–deficient mice. Quantitative computed tomography analysis showed that PAI-1 deficiency protected against streptozotocin-induced bone loss in female mice but not in male mice. PAI-1 deficiency blunted the changes in the levels of Runx2, osterix, and alkaline phosphatase in tibia as well as serum osteocalcin levels suppressed by the diabetic state in female mice only. Furthermore, the osteoclast levels in tibia, suppressed in diabetes, were also blunted by PAI-1 deficiency in female mice. Streptozotocin markedly elevated the levels of PAI-1 mRNA in liver in female mice only. In vitro study demonstrated that treatment with active PAI-1 suppressed the levels of osteogenic genes and mineralization in primary osteoblasts from female mouse calvaria. In conclusion, the current study indicates that PAI-1 is involved in the pathogenesis of type 1 diabetic osteoporosis in females. The expression of PAI-1 in the liver and the sensitivity of bone cells to PAI-1 may be an underlying mechanism.
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DOI：
10.1073/pnas.0602956103
发表时间：
2006-06-13
影响因子：
11.1
作者：
Le May, Cedric;Chu, Khoi;Mauvais-Jarvis, Franck
通讯作者：
Mauvais-Jarvis, Franck
影响因子：
6.2
作者：
Daci, E;Everts, V;Carmeliet, G
通讯作者：
Carmeliet, G
影响因子：
2
作者：
Follak, N;Klöting, I;Merk, H
通讯作者：
Merk, H
影响因子：
6.2
作者：
Nielsen, KL;Allen, MR;Heegaard, AM
通讯作者：
Heegaard, AM
影响因子：
15.9
作者：
Akune, T;Ohba, S;Kawaguchi, H
通讯作者：
Kawaguchi, H