Role of Macrophages and Plasminogen Activator Inhibitor-1 in Delayed Bone Repair in Diabetic Female Mice
Role of Macrophages and Plasminogen Activator Inhibitor-1 in Delayed Bone Repair in Diabetic Female Mice
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DOI：
10.1210/en.2018-00085
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发表时间：
2018-04-01
期刊：
影响因子：
4.8
通讯作者：
Kaji, Hiroshi
中科院分区：
文献类型：
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作者：
Shimoide, Takeshi;Kawao, Naoyuki;Kaji, Hiroshi
骨折延迟愈合是糖尿病患者的一个临床问题。然而，糖尿病延迟骨修复的机制仍不清楚。在这里，我们研究了链脲佐菌素（STZ）治疗和纤溶酶原激活物抑制剂-1（派-1）缺陷的雌性小鼠股骨损伤后，巨噬细胞在糖尿病延迟骨修复中的作用。在小鼠股骨损伤后第2天，STZ治疗显著降低了损伤部位F4/80阳性细胞（巨噬细胞）的数量，但不降低粒细胞分化抗原-1阳性细胞（中性粒细胞）的数量。在骨损伤后第2天，它显著降低了损伤部位巨噬细胞集落刺激因子、诱导型一氧化氮合酶（iNOS）、白细胞介素（IL）-6和CD 206的信使RNA（mRNA）水平。此外，STZ治疗减弱了由骨损伤诱导的骨髓中造血干细胞数量的减少。另一方面，派-1缺陷显著减弱了小鼠骨损伤后第2天STZ治疗诱导的损伤部位F4/80阳性细胞数量的减少。派-1缺乏并不影响它们，糖尿病小鼠受损股骨骨髓中F4/80和CD 11b双阳性细胞中iNOS和IL-6的RNA水平降低。派-1缺陷显著减弱糖尿病抑制的损伤部位的巨噬细胞的吞噬作用。总之，我们证明了1型糖尿病通过派-1降低了雌性小鼠股骨损伤后早期骨修复过程中受损部位巨噬细胞的积累和吞噬作用。
Delayed fracture healing is a clinical problem in diabetic patients. However, the mechanisms of diabetic delayed bone repair remain unknown. Here, we investigate the role of macrophages in diabetic delayed bone repair after femoral bone injury in streptozotocin (STZ)-treated and plasminogen activator inhibitor-1 (PAI-1)-deficient female mice. STZ treatment significantly decreased the numbers of F4/80-positive cells (macrophages) but not granulocyte-differentiation antigen-1-positive cells (neutrophils) at the damaged site on day 2 after femoral bone injury in mice. It significantly decreased the messenger RNA (mRNA) levels of macrophage colony-stimulating factor, inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and CD206 at the damaged site on day 2 after bone injury. Moreover, STZ treatment attenuated a decrease in the number of hematopoietic stem cells in bone marrow induced by bone injury. On the other hand, PAI-1 deficiency significantly attenuated a decrease in the number of F4/80-positive cells induced by STZ treatment at the damaged site on day 2 after bone injury inmice. PAI-1 deficiency did not affect them RNA levels of iNOS and IL-6 in F4/80- and CD11b-double-positive cells from the bone marrow of the damaged femurs decreased by diabetes in mice. PAI-1 deficiency significantly attenuated the phagocytosis of macrophages at the damaged site suppressed by diabetes. In conclusion, we demonstrated that type 1 diabetes decreases accumulation and phagocytosis of macrophages at the damaged site during early bone repair after femoral bone injury through PAI-1 in female mice.