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European Spine Journal

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01-10-2019 | Original Article

Endoplasmic reticulum stress regulates mechanical stress-induced ossification of posterior longitudinal ligament

Authors: Lei Shi, Jinhao Miao, Deyu Chen, Jiangang Shi, Yu Chen

Published in: European Spine Journal | Issue 10/2019

Abstract

Purpose

The pathogenesis of ossification of posterior longitudinal ligament (OPLL) is not completely clear. Previous study has confirmed a single-pass type I endoplasmic reticulum (ER) membrane protein kinase (PERK), which is a major transducer of the ER stress, participates in the process of OPLL in vitro. This study aimed to demonstrate the role of ER stress in mechanical stress (MS)-induced OPLL.

Methods

The posterior longitudinal ligaments were collected intraoperatively. The expression of ER stress markers in ligament tissue samples was compared between OPLL and non-OPLL patients in vivo. Ligament fibroblasts were isolated and cultured. Loaded by MS, the expression of ER stress markers in fibroblasts deriving from non-ossified areas of the ligament tissues from OPLL patients was detected. The influence of inhibition of ER stress on MS-induced OPLL and activation of mitogen-activated protein kinase (MAPK) pathways by MS was also investigated.

Results

We confirmed the ER stress markers were highly expressed in non-ossified areas of the ligament tissues from OPLL patients but could barely be detected in the ligaments from non-OPLL patients in vivo. We also found ER stress could be activated by MS during the process of OPLL in vitro. Moreover, inhibition of ER stress could hinder MS-induced OPLL and activation of MAPK signaling pathways by MS in vitro.

Conclusion

Activated ER stress was observed in OPLL patients both in vitro and in vivo. Mechanical stress could activate ER stress response in posterior longitudinal ligament fibroblasts and further promote OPLL in vitro. In this process, ER stress might work through the MAPK signaling pathways.

Graphic abstract

These slides can be retrieved under Electronic Supplementary Material.

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Title: Endoplasmic reticulum stress regulates mechanical stress-induced ossification of posterior longitudinal ligament
Authors: Lei Shi
Jinhao Miao
Deyu Chen
Jiangang Shi
Yu Chen
Publication date: 01-10-2019
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 10/2019
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-019-06074-2

At a glance: The STEP trials

Springer Medicine

Endoplasmic reticulum stress regulates mechanical stress-induced ossification of posterior longitudinal ligament

Abstract

Purpose

Methods

Results

Conclusion

Graphic abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Graphic abstract

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