Plasminogen Plays a Crucial Role in Bone Repair
Plasminogen Plays a Crucial Role in Bone Repair
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DOI：
10.1002/jbmr.1921
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发表时间：
2013-07-01
影响因子：
6.2
通讯作者：
Kaji, Hiroshi
中科院分区：
文献类型：
--
作者：
Kawao, Naoyuki;Tamura, Yukinori;Kaji, Hiroshi
为满足临床对骨重建的需求，有必要进一步开展骨再生的研究。纤溶酶原是组织纤溶系统的关键因子，它介导皮肤和肝脏的组织修复。然而，纤溶系统在骨再生中的作用仍不清楚。在这里，我们研究了纤溶酶原缺陷(PLG-/-)小鼠的骨修复和异位骨形成。与野生型(PLG+/+)小鼠不同，PLG-/-小鼠股骨的骨修复延迟。PLG-/-小鼠软骨基质沉积减少，成骨细胞形成减少。PLG-/-小鼠骨损伤部位血管形成、巨噬细胞聚集、血管内皮生长因子(VEGF)和转化生长因子-1(TGF-1)水平降低。相反，异位骨化在PLG+/+和PLG-/-小鼠之间没有显著差异。此外，在异位骨化中，PLG+/+和PLG-/-小鼠在血管生成、巨噬细胞聚集、血管内皮细胞生长因子和转化生长因子-α的水平上是相似的。我们的数据提供了新的证据，表明纤溶酶原在骨修复中是必不可少的。目前的研究表明，纤溶酶原参与了与巨噬细胞聚集、转化生长因子-β和血管内皮生长因子相关的血管生成，从而促进了骨修复。
The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver. However, the role of the fibrinolytic system in bone regeneration remains unknown. Herein, we investigated bone repair and ectopic bone formation using plasminogen-deficient (Plg-/-) mice. Bone repair of the femur is delayed in Plg-/- mice, unlike that in the wild-type (Plg+/+) mice. The deposition of cartilage matrix and osteoblast formation were both decreased in Plg-/- mice. Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor (VEGF) and transforming growth factor- (TGF-) were decreased at the site of bone damage in Plg-/- mice. Conversely, heterotopic ossification was not significantly different between Plg+/+ and Plg-/- mice. Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF- were comparable between Plg+/+ and Plg-/- mice in heterotopic ossification. Our data provide novel evidence that plasminogen is essential for bone repair. The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF-, and VEGF, thereby leading to the enhancement of bone repair.