Association of Neutrophil Extracellular Traps with the Development of Idiopathic Osteonecrosis of the Femoral Head
Association of Neutrophil Extracellular Traps with the Development of Idiopathic Osteonecrosis of the Femoral Head
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DOI：
10.1016/j.ajpath.2020.07.008
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发表时间：
2020-11-01
影响因子：
6
通讯作者：
Ishizu, Akihiro
中科院分区：
文献类型：
--
作者：
Nonokawa, Mayu;Shimizu, Tomohiro;Ishizu, Akihiro
特发性股骨头坏死（ONFH）被定义为股骨头非创伤性缺血引起的骨细胞坏死。医源性糖皮质激素的使用和习惯性饮酒被认为是危险因素。有研究表明，糖皮质激素诱导的血小板活化有助于股骨头局部血流紊乱。活化血小板和酒精均可诱导中性粒细胞胞外陷阱（NETs）。为了确定NETs与特发性ONFH发展的关系，通过免疫荧光染色评估特发性ONFH和骨关节炎患者手术切除的股骨头是否存在net形成的中性粒细胞。特发性ONFH患者股骨头周围的小血管中存在形成net的中性粒细胞，但骨关节炎患者没有。此外，Wistar-Kyoto大鼠静脉注射NET形成的中性粒细胞或未NET诱导的中性粒细胞，然后用免疫组织化学缺氧诱导因子-1 α评价股骨头周围组织的缺血状态。形成NET的中性粒细胞循环进入股骨头周围组织，组织中缺氧诱导因子-1 α的表达高于未形成NET的中性粒细胞静脉注射的大鼠。此外，在大鼠股骨头内静脉注射形成net的中性粒细胞，观察到骨细胞的缺血性改变。这些研究结果表明，NETs可能与特发性ONFH的发展有关。
Idiopathic osteonecrosis of the femoral head (ONFH) is defined as necrosis of osteocytes due to a non-traumatic ischemia of the femoral head. Iatrogenic glucocorticoid administration and habitual alcohol intake are regarded as risk factors. It has been suggested that glucocorticoid-induced activation of platelets contributes to the local blood flow disturbance of the femoral head. Both activated platelets and alcohol can induce neutrophil extracellular traps (NETs). To determine the association of NETs with the development of idiopathic ONFH, surgically resected femoral heads of patients with idiopathic ONFH and osteoarthritis were assessed for existence of NET-forming neutrophils by immunofluorescence staining. NET-forming neutrophils were present in small vessels surrounding the femoral head of patients with idiopathic ONFH but not osteoarthritis. Moreover, Wistar-Kyoto rats were intravenously injected with NET-forming neutrophils or neutrophils without NET induction, and then the ischemic state of the tissue around the femoral head was evaluated by immunohistochemistry for hypoxia-inducible factor-1 alpha. NET-forming neutrophils circulated into the tissue around the femoral head, and hypoxia-inducible factor-1 alpha expression in the tissue was higher compared with that of rats intravenously administered with neutrophils without NET induction. Furthermore, ischemic change of osteocytes was observed in the femoral head of rats given an i.v. injection of NET-forming neutrophils. The collective findings suggest that NETs are possibly associated with the development of idiopathic ONFH.