Department of Oral Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.
Department of Prosthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.
Sci Rep. 2017 Aug 22;7(1):9027. doi: 10.1038/s41598-017-09210-4.
Repair of large bone defects remains a challenge for surgeons, tissue engineering represents a promising approach. However, the use of this technique is limited by delayed vascularization in central regions of the scaffold. Growth differentiation factor 15(GDF15) has recently been reported to be a potential angiogenic cytokine and has an ability to promote the proliferation of human umbilical vein endothelial cells(HUVECs). Whether it can be applied for promoting vascularized bone regeneration is still unknown. In this study, we demonstrated that GDF15 augmented the expression of cyclins D1 and E, induced Rb phosphorylation and E2F-1 nuclear translocation, as well as increased HUVECs proliferation. Furthermore, we also observed that GDF15 promoted the formation of functional vessels at an artificially-induced angiogenic site, and remarkably improved the healing in the repair of critical-sized calvarial defects. Our results confirm the essential role of GDF15 in angiogenesis and suggest its potential beneficial use in regenerative medicine.
修复大骨缺损仍然是外科医生面临的挑战，组织工程代表了一种很有前途的方法。然而，该技术的应用受到支架中心区域血管化延迟的限制。生长分化因子 15（GDF15）最近被报道为一种潜在的血管生成细胞因子，具有促进人脐静脉内皮细胞（HUVEC）增殖的能力。它是否可用于促进血管化骨再生尚不清楚。在这项研究中，我们证明 GDF15 可增强细胞周期蛋白 D1 和 E 的表达，诱导 Rb 磷酸化和 E2F-1 核易位，并增加 HUVEC 增殖。此外，我们还观察到 GDF15 可促进人工诱导的血管生成部位功能性血管的形成，并显著改善临界尺寸颅骨缺损修复中的愈合。我们的结果证实了 GDF15 在血管生成中的重要作用，并表明其在再生医学中具有潜在的有益用途。
