PDF(Pubmed)
Abstract：
Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium\'s protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.
摘要：
自噬可能在糖皮质激素性股骨头坏死(GC-ONFH)的发生发展中起重要作用。锂是一种经典的自噬调节剂，锂还可以激活成骨途径，使其成为GC-ONFH的极具前景的治疗剂。我们旨在评估锂对GC-ONFH的潜在治疗作用。对于体外实验，用大鼠原代成骨细胞研究锂对GC诱导的自噬水平和成骨活性功能障碍的保护作用的潜在机制。对于体内实验，使用GC-ONFH大鼠模型评估口服锂对GC-ONFH的治疗效果及其潜在机制。结果表明，GC过度激活成骨细胞的自噬并降低其成骨活性。锂通过PI3K/AKT/mTOR信号通路减少GC处理的成骨细胞过度激活的自噬，并增加其成骨活性。口服锂可降低GC-ONFH大鼠模型的骨坏死率，并通过PI3K/AKT/mTOR信号通路抑制骨组织中自噬相关蛋白的表达。总之,锂可以通过激活PI3K/AKT/mTOR信号通路来抑制过度激活的自噬，并上调GC诱导的成骨细胞和GC-ONFH大鼠模型中骨形成基因的表达。锂可能是GC-ONFH的有前途的治疗剂。然而,自噬在GC-ONFH发病机制中的作用仍存在争议。自噬在GC-ONFH发病机制中的作用仍需进一步研究。以及锂在GC-ONFH治疗中的功效及其潜在机制。
