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.

Calcium Phosphate Cement Causes Nucleus Pulposus Cell Degeneration Through the ERK Signaling Pathway

“…Regarding the biological level of whether or how bone cement particles may induce IDD, which is the main aim of our study, our group has previously done some research on the biological mechanism of how PMMA particles induce HNPCs’ degeneration [ 29 ]. That study revealed the role of PMMA particles in inducing IVD degeneration by downregulating CTGF through Hippo/YAP pathway.…”

Melatonin Protects Intervertebral Disc from Degeneration by Improving Cell Survival and Function via Activation of the ERK1/2 Signaling Pathway

“…No.4800). Cell culture was performed as described in the protocol in our previous study [22]. Cells preserved in liquid nitrogen were quickly thawed in a preheated water bath (37°C) for 2 min.…”

“…Cell viability of NPCs was determined at 24 h and 96 h after the induction with 0.1, 0.5, 1, 5, 10, 50, and 100 μ M melatonin. The measurement procedure was as described in our previous study [22]: 10 μ L of Cell Counting Kit-8 (CCK-8) solution (Dojindo, Tokyo, Japan) was added to each well and the 96-well plates were incubated for 1 h at 37°C and 5% CO 2 . After that, the supernatants were carefully aspirated.…”

“…Propidium iodide (PI) staining was used to analyze cell cycle distribution as described in our previous study [22]. NPCs were digested by trypsin and centrifuged at 3000 rpm for 5 min.…”

“…NPCs were treated with different concentrations of melatonin for 24 h before harvest. We follow the protocol in our previous study [22]. The cells were washed with 4°C PBS prior to being resuspended in a total volume of 500 μ L binding buffer.…”