eCM (Eur Cell Mater / e Cells & Materials) Not-for-Profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2021   Volume No 45 – pages 31-45

Title: Uniaxial cyclic stretch enhances osteogenic differentiation of OPLL-derived primary cells via YAP-Wnt/β-catenin axis

Authors:  Z Zhu, T Tang, Z He, F Wang, H Chen, G Chen, J Zhou, S Liu, J Wang, W Tian, D Chen, X Wu, X Liu, Z Zhou, S Liu

Address: Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Orthopaedic Research Institute/Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

E-mail: Liuxizhe at

Abstract: The pathogenesis of posterior longitudinal ligament ossification (OPLL) remains inadequately understood. Mechanical stimulation is one of the important pathogenic factors in OPLL. As one of the mechanical stimulation transduction signals, the yes-associated protein (YAP) interacts with the Wnt/β-catenin signalling pathway, which plays an important role in osteogenic differentiation. This study aimed to demonstrate the role of YAP-Wnt/β-catenin axis in cell differentiation induced by mechanical stress. Primary cells extracted from posterior longitudinal ligament tissues from OPLL or non-OPLL patients were subjected to sinusoidal uniaxial cyclic stretch (5 %, 0.5 Hz, 3 d). The expression of runt-related transcription factor 2, collagen I, osterix, osteocalcin and alkaline phosphatase were compared between the static and the experimental groups. In addition, the cytoskeleton was detected using phalloidin staining while YAP phosphorylation states and nuclear location were identified using immunofluorescence. The results showed that mechanical stretching loading increased the expression of osteogenic genes and proteins in the OPLL group, while it had no significant effect on the control group. When OPLL cells were stretched, YAP exhibited an obvious nuclear translocation and the Wnt/β-catenin pathway was activated. Knocking down YAP or β-catenin could weaken the impact upon osteogenic differentiation induced by mechanical stimulation. YAP-mediated mechanical stimulation promoted osteogenic differentiation of OPLL cells through Wnt/β-catenin pathway and this progress was independent of the Hippo pathway.

Keywords: Ossification of the posterior longitudinal ligament (OPLL), mechanotransduction, heterotopic ossification, yes-associated protein (YAP), cytoskeleton remodelling, Wnt/β-catenin signalling.

Publication date: February 7th 2023

Article download: Pages 31-45 (PDF file)

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