PMMA Bone Cement Acts on the Hippo/YAP Pathway To Regulate CTGF and Induce Intervertebral Disc Degeneration.

Abstract

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.