Dai Junwei, Tao Jun, Wei Shusheng, Han Baokun, Ma Shuai, Wu Chengyu, Sun Long, Ma Xiaodong, Chen Yimeng
Department of Orthopedic, The First Hospital of Anhui University of Science and Technology, Huainan, Anhui, P.R. China.
Department of Orthopedic, The First people Hospital of Wuhu, Wuhu, Anhui, P.R. China.
Ann Med Surg (Lond). 2025 Jul 18;87(9):5494-5502. doi: 10.1097/MS9.0000000000003615. eCollection 2025 Sep.
This study aimed to investigate the role of natural killer (NK) cells in the RANKL/RANK/OPG pathway in osteonecrosis of the femoral head (ONFH). C57 mice were categorized into a control group, an observation group (10 mice each), and an experimental group comprising 4 NK cell knockout mice. A hormone-induced femoral head necrosis model was created by administering lipopolysaccharide combined with methylprednisolone for 8 weeks to the experimental and control groups. The observation group received subcutaneous injections of an equal amount of normal saline. After 8 weeks, peripheral blood was collected from the mice, and bilateral femoral head specimens were obtained post-mortem. Expression levels of NK cells, OPG, RANK, and RANKL in the peripheral blood and joint fluid of ONFH mice were determined using PCR and ELISA techniques, and compared with the control group. The experimental group exhibited an increased number of NK cells in the peripheral blood and joint fluid compared to the control group. OPG expression was downregulated, while RANK and RANKL were significantly upregulated, resulting in a marked increase in the number of mature osteoclasts. In ONFH patients, NK cells were found to upregulate TNF-α and RANKL, downregulate IFN-γ and OPG, promote osteoclast maturation, disrupt bone balance, accelerate femoral head necrosis collapse, and ultimately hasten the progression of femoral head necrosis.
本研究旨在探讨自然杀伤（NK）细胞在股骨头坏死（ONFH）的RANKL/RANK/OPG通路中的作用。将C57小鼠分为对照组、观察组（每组10只）和实验组，实验组包含4只NK细胞敲除小鼠。通过对实验组和对照组小鼠注射脂多糖联合甲基泼尼松龙8周，建立激素诱导的股骨头坏死模型。观察组皮下注射等量生理盐水。8周后，采集小鼠外周血，并在处死后获取双侧股骨头标本。采用PCR和ELISA技术测定ONFH小鼠外周血和关节液中NK细胞、OPG、RANK和RANKL的表达水平，并与对照组进行比较。与对照组相比，实验组外周血和关节液中NK细胞数量增加。OPG表达下调，而RANK和RANKL显著上调，导致成熟破骨细胞数量明显增加。在ONFH患者中，发现NK细胞上调TNF-α和RANKL，下调IFN-γ和OPG，促进破骨细胞成熟，破坏骨平衡，加速股骨头坏死塌陷，最终加速股骨头坏死的进展。
