磷酸西他列汀
巨噬细胞极化
血管生成
链脲佐菌素
体内
骨整合
巨噬细胞
内分泌学
内科学
脐静脉
化学
糖尿病
药理学
医学
体外
2型糖尿病
植入
生物
生物化学
外科
生物技术
作者
Xianguo Geng,Xinyi Huang,Tianji Wang,Jing Wang,Guoxuan Zhao,Han Wang,Feng Yan,Wei Lei,Xiaofan Hu
标识
DOI:10.1016/j.biopha.2020.110078
摘要
Clinical evidence indicates that sitagliptin treatment improves bone quality in diabetic patients, but the mechanisms involved remain elusive. Here, we studied the role of angiogenesis with sitagliptin treatment in diabetes-induced poor osteointegration of titanium implants and the underlying mechanisms. In vitro, Human Umbilical Vein Endothelial Cells (HUVECs) incubated on titanium (Ti) surface were subjected to 1) normal milieu (NM); 2) diabetic milieu (DM); 3) DM + sitagliptin; 4) NM + macrophage; 5) DM + macrophage; or 6) DM + macrophage + sitagliptin. Microphage and HUVECs were cultured alone or co-cultured in a Transwell system. In vivo, DM was induced by high-fat diet and administration of streptozotocin (STZ) in rats. Titanium screws were implanted in the femurs of rats in three groups: Control, DM, Sitagliptin-treated DM. In vitro, when cells were incubated alone, DM caused M1 polarization of macrophage, evidenced by the increased iNOS and decreased CD206 expressions, and obvious dysfunctions of HUVECs. The DM-induced injury of endothelial cells were significantly worsened when the two cells were co-cultured. The addition of sitagliptin markedly reversed the changes of macrophage but not of HUVECs in DM when cells were cultured alone. When cells co-cultured, however, both the abnormal macrophage polarization and the endothelial impairment in DM was significantly alleviated by sitagliptin. In vivo, compared with normal animals, DM animals showed imbalanced M1/M2 polarization, angiogenesis inhibition and poor bone formation on the bone-implant interface (BII), which were significantly ameliorated by sitagliptin treatment. Our results demonstrate macrophage polarization imbalance as a crucial mechanism underlying the impaired angiogenesis and bone healing in diabetes, and provide sitagliptin as a promising novel drug for biomaterial-engineering to improve the osteointegration of titanium implants in diabetic patients.
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