Plasminogen activator inhibitor-1 is involved in impaired bone repair associated with diabetes in female mice.
Plasminogen activator inhibitor-1 is involved in impaired bone repair associated with diabetes in female mice.
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DOI：
10.1371/journal.pone.0092686
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kaji H
中科院分区：
文献类型：
--
作者：
Mao L;Kawao N;Tamura Y;Okumoto K;Okada K;Yano M;Matsuo O;Kaji H
先前的研究表明糖尿病患者骨折愈合受损;然而，其潜在机制仍不清楚。在这里，我们研究了纤溶酶原激活物抑制剂-1（派-1）在受损的骨修复过程中的作用，通过使用链脲佐菌素（STZ）诱导的糖尿病雌性野生型（派-1 +/+）和派-1缺陷型（派-1 −/−）小鼠。在未接受STZ治疗的派-1 +/+和派-1 −/−小鼠中，股骨损伤部位的骨修复和碱性磷酸酶（ALP）阳性细胞数量相当。虽然STZ治疗派-1 +/+小鼠的骨修复过程被延迟，但这种延迟的骨修复在派-1 −/−小鼠中被钝化。与派-1 +/+小鼠相比，派-1 −/−小鼠中STZ治疗诱导的骨损伤部位ALP阳性细胞数量减少减弱。另一方面，派-1缺乏增加了有或没有STZ治疗的雌性小鼠中ALP和I型胶原mRNA的水平，并且在派-1 +/+小鼠中被糖尿病状态抑制的Osterix和骨钙素mRNA的水平在派-1 −/−小鼠中得到部分保护。派-1缺乏并不影响软骨基质的形成和II型和X型胶原蛋白和聚集蛋白聚糖mRNA的水平抑制STZ治疗，虽然派-1缺乏增加了小鼠的软骨形成标记物的表达，而没有STZ治疗。目前的研究表明，派-1参与了受损的骨修复过程中诱导的糖尿病状态，部分通过减少ALP阳性细胞的数量。
Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1 +/+) and PAI-1-deficient (PAI-1 −/−) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1 +/+ and PAI-1 −/− mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1 +/+ mice, this delayed bone repair was blunted in PAI-1 −/− mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1 −/− mice compared to PAI-1 +/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1 +/+ mice, were partially protected in PAI-1 −/− mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells.
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影响因子：
4.2
作者：
Rundle, Charles H.;Wang, Xiaoguang;Lau, K. -H. William
通讯作者：
Lau, K. -H. William
影响因子：
6.2
作者：
Daci, E;Udagawa, N;Carmeliet, G
通讯作者：
Carmeliet, G
影响因子：
4.1
作者：
Gandhi, A;Beam, HA;Lin, SS
通讯作者：
Lin, SS
影响因子：
6
作者：
Lerman, OZ;Galiano, RD;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
16.2
作者：
Fadini GP;Albiero M;Vigili de Kreutzenberg S;Boscaro E;Cappellari R;Marescotti M;Poncina N;Agostini C;Avogaro A
通讯作者：
Avogaro A