Lei Shi1, Jinhao Miao1, Deyu Chen1, Jiangang Shi1, Yu Chen2. 1. Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, No 415, Fengyang Road, Huangpu District, Shanghai, China. 2. Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, No 415, Fengyang Road, Huangpu District, Shanghai, China. cyspine@smmu.edu.cn.
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. These slides can be retrieved under Electronic Supplementary Material.
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-OPLLpatients 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 OPLLpatients 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 OPLLpatients but could barely be detected in the ligaments from non-OPLLpatients 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 OPLLpatients 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. These slides can be retrieved under Electronic Supplementary Material.
Entities:
Keywords:
Endoplasmic reticulum stress; Mechanical stress; Mitogen-activated protein kinase; Ossification of posterior longitudinal ligament; PERK
Authors: Long He; Junwon Lee; Jae Hyuk Jang; Krisada Sakchaisri; Joonsung Hwang; Hyun Joo Cha-Molstad; Kyung A Kim; In Ja Ryoo; Hee Gu Lee; Sun Ok Kim; Nak Kyun Soung; Kyung Sang Lee; Yong Tae Kwon; Raymond Leo Erikson; Jong Seog Ahn; Bo Yeon Kim Journal: Cell Signal Date: 2012-11-23 Impact factor: 4.315