Zhang Chen, Li Miao, Ma Jun, Zhang Eryang, Ban Wenrui, Lü Leifeng, Dang Xiaoqian, Wang Kunzheng
The First Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710004, P.R.China.
Department of Ultrasound, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi, 710004, P.R.China.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2016 Jun 8;30(6):661-668. doi: 10.7507/1002-1892.20160135.
To investigate the effect of Wnt/β-catenin signal pathway on the apoptosis in steroid-induced avascular necrosis of femoral head (SANFH) in rats.
Seventy-two male Sprague Dawley rats (weighing, 200-230 g) were randomly divided into the control group (group A, =24), the model group (group B, =24), and the intervening group (group C, =24). The rats in groups B and C were injected with lipopolysaccharide and methylprednisolone (MPS) to establish the SANFH model. The rats in group C were injected intramuscularly with human recombinant secreted frizzled related protein 1 (SFRP1) [1 μg/(kg·d)] at the first time of MPS administration for 30 days. The rats in group A received saline injection at the same injection time of group B. The general condition of rats in groups B and C was observed during modeling and after modeling. At 2, 4, and 8 weeks after last injection of MPS, 8?rats were sacrificed to harvest the femoral head. Histological staining was performed to evaluate osteonecrosis. Apoptosis was detected via TUNEL staining. The expressions of Wnt/β-cate nin pathway signaling molecules (activated β-catenin and c-Myc) were detected by immunohistochemistry and Western blot.
Six rats were added in groups B and C because of 6 deaths. The other rats survived to the end of experiment. Normal bone structure was observed in group A; osteonecrosis of bone structure disturbance and disruption of the trabecula were found with time in groups B and C. Group C had the highest empty lacuna rate and apoptosis rate, followed by groups B and A, showing significant difference between groups ( < 0.05). The expression levels of activated β-catenin and c-Myc were significantly lower in group C than groups A and B ( < 0.05), and in group B than group A ( < 0.05).
Wnt/β-catenin signal pathway is involved in the pathogenesis in early SANFH model and its?possible mechanism?is to affect the cell cycle and cell apoptosis by the regulation of c-Myc expression.
探讨Wnt/β-连环蛋白信号通路对大鼠激素性股骨头缺血性坏死（SANFH）中细胞凋亡的影响。
将72只雄性Sprague Dawley大鼠（体重200 - 230 g）随机分为对照组（A组，n = 24）、模型组（B组，n = 24）和干预组（C组，n = 24）。B组和C组大鼠注射脂多糖和甲基强的松龙（MPS）建立SANFH模型。C组大鼠在首次给予MPS时肌肉注射人重组分泌型卷曲相关蛋白1（SFRP1）[1 μg/(kg·d)]，共30天。A组大鼠在与B组相同的注射时间给予生理盐水注射。在建模期间及建模后观察B组和C组大鼠的一般情况。在最后一次注射MPS后2、4和8周，处死8只大鼠以获取股骨头。进行组织学染色以评估骨坏死情况。通过TUNEL染色检测细胞凋亡。采用免疫组织化学和蛋白质印迹法检测Wnt/β-连环蛋白通路信号分子（活化的β-连环蛋白和c-Myc）的表达。
B组和C组因6只大鼠死亡而分别补充6只大鼠。其他大鼠存活至实验结束。A组观察到正常骨结构；B组和C组随时间推移出现骨结构紊乱和骨小梁破坏的骨坏死。C组空骨陷窝率和凋亡率最高，其次为B组和A组，组间差异有统计学意义（P < 0.05）。C组活化的β-连环蛋白和c-Myc的表达水平显著低于A组和B组（P < 0.05），且B组低于A组（P < 0.05）。
Wnt/β-连环蛋白信号通路参与早期SANFH模型的发病机制，其可能机制是通过调节c-Myc表达影响细胞周期和细胞凋亡。
