Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an710004, Shaanxi Province, People's Republic of China.
Department of Orthopaedics, First Affiliated Hospital of Xi'an Jiaotong University, School of Medicine, No. 277 Yanta Road, Xian, 710061, China.
Sci Rep. 2017 Sep 20;7(1):11928. doi: 10.1038/s41598-017-12196-8.
Nuclear factor-kappa B (NF-κB) interactively affects the Wnt/β-catenin pathway and is closely related to different diseases. However, such crosstalk effect in steroid-associated necrosis of femoral head (SANFH) has not been fully explored and evaluated. In this study, early-stage SANFH was induced by two doses of lipopolysaccharide (LPS, 2 mg/kg/day) and three doses of methylprednisolone (MPS, 40 mg/kg/day). LPS and pyrrolidine dithiocarbamate (PDTC) were administered to activate the TLR4/NF-κB pathway and selectively block the activation of NF-κB, respectively. Results showed that PDTC treatment significantly reduced NF-κB expression, diminished inflammation, and effectively decreased bone resorption processes (osteoclastogenesis, adipogenesis, and apoptosis), which were evidently reinforced after osteonecrosis induction. Moreover, PDTC remarkably increased the interfered Wnt/β-catenin pathway and elevated bone formation processes (osteogenesis and angiogenesis). Ultimately, PDTC treatment effectively reduced the incidence of SANFH. Therefore, the excessive activation of TLR4/NF-κB may interactively suppress the Wnt/β-catenin pathway and induce SANFH. Hence, we propose NF-κB-targeted treatment as a novel therapeutic strategy for SANFH.
核因子-κB（NF-κB）与 Wnt/β-连环蛋白通路相互作用，并与多种疾病密切相关。然而，在激素相关性股骨头坏死（SANFH）中，这种串扰效应尚未得到充分的探索和评估。在这项研究中，通过给予两剂脂多糖（LPS，2mg/kg/天）和三剂甲泼尼龙（MPS，40mg/kg/天）来诱导早期 SANFH。LPS 和吡咯烷二硫代氨基甲酸盐（PDTC）分别用于激活 TLR4/NF-κB 通路和选择性地阻断 NF-κB 的激活。结果表明，PDTC 治疗可显著降低 NF-κB 的表达，减轻炎症，并有效减少破骨细胞形成、脂肪生成和凋亡等骨吸收过程，这些过程在骨坏死诱导后明显增强。此外，PDTC 显著增加了受干扰的 Wnt/β-连环蛋白通路，并提高了成骨和血管生成等骨形成过程。最终，PDTC 治疗有效地降低了 SANFH 的发生率。因此，TLR4/NF-κB 的过度激活可能会相互抑制 Wnt/β-连环蛋白通路并导致 SANFH。因此，我们提出 NF-κB 靶向治疗作为 SANFH 的一种新的治疗策略。
