Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
J Bone Miner Res. 2013 Jul;28(7):1561-74. doi: 10.1002/jbmr.1921.
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-β (TGF-β) 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-β 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-β, and VEGF, thereby leading to the enhancement of bone repair.
为满足骨骼重建的临床需求，有必要进一步研究骨骼再生。纤溶酶原是组织纤维蛋白溶解系统的关键因素，可介导皮肤和肝脏的组织修复。然而，纤维蛋白溶解系统在骨骼再生中的作用尚不清楚。在此，我们使用纤溶酶原缺陷（Plg⁻/⁻）小鼠研究了骨骼修复和异位骨形成。与野生型（Plg⁺/⁺）小鼠不同，Plg⁻/⁻小鼠的股骨修复被延迟。Plg⁻/⁻小鼠的软骨基质沉积和成骨细胞形成均减少。Plg⁻/⁻小鼠骨骼损伤部位的血管形成、巨噬细胞聚集以及血管内皮生长因子（VEGF）和转化生长因子-β（TGF-β）的水平降低。相反，Plg⁺/⁺和 Plg⁻/⁻小鼠的异位骨化之间没有显著差异。此外，在异位骨化中，Plg⁺/⁺和 Plg⁻/⁻小鼠的血管生成、巨噬细胞聚集以及 VEGF 和 TGF-β的水平相当。我们的数据提供了新的证据，表明纤溶酶原对于骨骼修复是必不可少的。本研究表明，纤溶酶原有助于与巨噬细胞聚集、TGF-β和 VEGF 相关的血管生成，从而增强骨骼修复。
