The impact of sitagliptin on macrophage polarity and angiogenesis in the osteointegration of titanium implants in type 2 diabetes

Biomedicine & Pharmacotherapy

Xiaofan Hu¹  Wei Lei²  Xinyi Huang³  Yafei Feng³  Tianji Wang³  Geng Xiang³  Jing Wang³  Guoxuan Zhao³  Han Wang³ 

[1] Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, China;Corresponding authors.;Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, China;

关键词: Angiogenesis;    Diabetes;    Macrophage polarization;    Sitagliptin;    Titanium implants;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

【 授权许可】

Unknown