Previous studies have shown that the tumor necrosis factor‐α (TNF‐α) levels in serum and bone tissues formed in avascular necrosis of femoral head (ANFH) patients were higher than those of normal individuals, indicating TNF‐α might play a role in the pathogenesis of ANFH. However, the underlying mechanisms remain unclear. Hematoxylin and eosin staining was performed to show the pathological changes of ANFH bone tissues. TNF‐α expression in normal and ANFH tissues was examined by quantitative real‐time polymerase chain reaction and western blot analyses. Osteoblast autophagy and apoptosis, as well as signaling pathways activation, were measured by their corresponding marker proteins. Osteoblast proliferation, autophagy, and apoptosis were evaluated using cell counting kit‐8, transmission electron microscopy, and flow cytometry. The structures of bone tissues of ANFH were obviously damaged. TNF‐α expression was significantly upregulated in ANFH bone tissues compared to normal tissues. Autophagy and apoptosis were remarkably promoted, and p38 mitogen‐activated protein kinase (MAPK)/nuclear factor‐κB (NF‐κB) signaling pathways were markedly activated in ANFH. Suppression of the p38 MAPK/NF‐κB pathway significantly attenuated the TNF‐α‐induced autophagy, however, enhanced the TNF‐α‐induced apoptosis in osteoblasts. Increased TNF‐α in ANFH regulated osteoblast autophagy and apoptosis by p38 MAPK/NF‐κB signaling pathways, blocking the pathway by inhibitors exacerbated TNF‐α‐induced apoptosis through impairing autophagy flux.

中文翻译：

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TNF-α通过p38 MAPK /NF-κB信号通路介导成骨细胞自噬和细胞凋亡，从而调节股骨头坏死的早期发展。

先前的研究表明，股骨头缺血性坏死（ANFH）患者的血清和骨组织中的肿瘤坏死因子-α（TNF-α）水平高于正常人，表明TNF-α可能与ANFH的发病机理。但是，其潜在机制仍不清楚。进行苏木精和曙红染色以显示ANFH骨组织的病理变化。通过定量实时聚合酶链反应和蛋白质印迹分析检查了正常和ANFH组织中的TNF-α表达。成骨细胞的自噬和细胞凋亡以及信号通路的激活，通过其相应的标记蛋白进行了测定。使用细胞计数试剂盒-8，透射电子显微镜和流式细胞仪评估成骨细胞的增殖，自噬和凋亡。ANFH的骨组织结构明显受损。与正常组织相比，ANFH骨组织中的TNF-α表达明显上调。显着促进自噬和细胞凋亡，并且在ANFH中明显激活了p38丝裂原活化蛋白激酶（MAPK）/核因子κB（NF-κB）信号通路。p38 MAPK /NF-κB通路的抑制显着减弱了TNF-α诱导的自噬，但增强了TNF-α诱导的成骨细胞凋亡。ANFH中的TNF-α升高通过p38 MAPK /NF-κB信号传导通路调节成骨细胞自噬和凋亡，通过抑制剂阻断该通路通过损害自噬通量加剧了TNF-α诱导的凋亡。显着促进自噬和细胞凋亡，并且在ANFH中明显激活了p38丝裂原活化蛋白激酶（MAPK）/核因子κB（NF-κB）信号通路。p38 MAPK /NF-κB通路的抑制显着减弱了TNF-α诱导的自噬，但增强了TNF-α诱导的成骨细胞凋亡。ANFH中的TNF-α升高通过p38 MAPK /NF-κB信号传导通路调节成骨细胞自噬和凋亡，通过抑制剂阻断该通路通过损害自噬通量加剧了TNF-α诱导的凋亡。显着促进自噬和细胞凋亡，并且在ANFH中明显激活了p38丝裂原活化蛋白激酶（MAPK）/核因子κB（NF-κB）信号通路。p38 MAPK /NF-κB通路的抑制显着减弱了TNF-α诱导的自噬，但增强了TNF-α诱导的成骨细胞凋亡。ANFH中的TNF-α升高通过p38 MAPK /NF-κB信号传导通路调节成骨细胞自噬和凋亡，通过抑制剂阻断该通路通过损害自噬通量加剧了TNF-α诱导的凋亡。增强TNF-α诱导的成骨细胞凋亡。ANFH中的TNF-α升高通过p38 MAPK /NF-κB信号传导通路调节成骨细胞自噬和凋亡，通过抑制剂阻断该通路通过损害自噬通量加剧了TNF-α诱导的凋亡。增强TNF-α诱导的成骨细胞凋亡。通过p38 MAPK /NF-κB信号通路增加ANFH中的TNF-α调节成骨细胞自噬和凋亡，通过抑制剂阻断该通路通过损害自噬通量加剧TNF-α诱导的凋亡。