Ge Jun, Yang Huilin, Chen Yufeng, Yan Qi, Wu Cenhao, Zou Jun
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
ACS Biomater Sci Eng. 2019 Jul 8;5(7):3293-3302. doi: 10.1021/acsbiomaterials.9b00146. Epub 2019 Jun 4.
Kyphoplasty is a novel approach treating osteoporotic vertebral compression fractures and poly(methyl methacrylate) (PMMA) is the most common bone cement used for kyphoplasty. Cement leaked into an intervertebral disc (IVD) usually causes problems. Herein, we explored the effects of PMMA particles on the biological behavior of nucleus pulposus cells and proved the inhibiting effect of PMMA particles in a dose-dependent manner. Besides, PMMA particles led to cell cycle arrest and the abnormal expression of several apoptosis associated gene. Futhermore, we found PMMA particles upregulated the expression of p-Mst1/2, p-Lats1, and p-YAP, whereas they downregulated the expression of YAP and CTGF, suggesting the activing effect on the Hippo/YAP/CTGF signaling pathway. By overexpression of YAP, PMMA-induced nucleus pulposus cell degeneration was reversed. In vivo study also showed that recombinant CTGF protein could alleviate PMMA-induced IVD degeneration in rats. To sum up, our study revealed the role of PMMA particles in inducing IVD degeneration by downregulating CTGF through Hippo/YAP pathway.
椎体后凸成形术是治疗骨质疏松性椎体压缩骨折的一种新方法，聚甲基丙烯酸甲酯（PMMA）是椎体后凸成形术中最常用的骨水泥。骨水泥渗漏到椎间盘（IVD）通常会引发问题。在此，我们探讨了PMMA颗粒对髓核细胞生物学行为的影响，并证明了PMMA颗粒具有剂量依赖性抑制作用。此外，PMMA颗粒导致细胞周期停滞以及多个凋亡相关基因的异常表达。此外，我们发现PMMA颗粒上调了p-Mst1/2、p-Lats1和p-YAP的表达，而下调了YAP和CTGF的表达，提示其对Hippo/YAP/CTGF信号通路具有激活作用。通过YAP过表达，PMMA诱导的髓核细胞退变得以逆转。体内研究还表明，重组CTGF蛋白可减轻PMMA诱导的大鼠椎间盘退变。综上所述，我们的研究揭示了PMMA颗粒通过Hippo/YAP途径下调CTGF在诱导椎间盘退变中的作用。
