nach oben

European Spine Journal

Erschienen in:

19.07.2019 | Original Article

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

verfasst von: Lei Shi, Jinhao Miao, Deyu Chen, Jiangang Shi, Yu Chen

Erschienen in: European Spine Journal | Ausgabe 10/2019

Einloggen, um Zugang zu erhalten

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.

Nur mit Berechtigung zugänglich

Karner CM, Lee SY, Long F (2017) Bmp induces osteoblast differentiation through both Smad4 and mTORC1 signaling. Mol Cell Biol 37(4):1–12CrossRef

He L, Lee J, Jang JH et al (2013) Osteoporosis regulation by salubrinal through elF2α mediated differentiation of osteoclast and osteoblast. Cell Signal 25(2):552–560CrossRef

Choi YH, Kim YJ, Jeong HM et al (2014) Akt enhances Runx2 protein stability by regulating Smurf2 function during osteoblast differentiation. FEBS J 281(16):3656–3666CrossRef

Wysokinski D, Pawlowska E, Blasiak J (2015) RUNX2: a master bone growth regulator that may be involved in the DNA damage response. DNA Cell Biol 34(5):305–315CrossRef

Chen Y, Gao H, Yin Q et al (2013) ER stress activating ATF4/CHOP-TNF alpha signaling pathway contributes to alcohol-induced disruption of osteogenic lineage of multipotential mesenchymal stem cell Cellular physiology and biochemistry. Cell Physiol Biochem 32(3):743–754CrossRef

Komori T (2016) Glucocorticoid signaling and bone biology. Horm Metab Res 48(11):755–763CrossRef

Kondo S, Onari K, Watanabe K et al (2001) Hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification: a cervical myelopathy case report. Spine 26(1):110–114CrossRef

Yokosuka K, Park JS, Jimbo K et al (2007) Immunohistochemical demonstration of advanced glycation end products and the effects of advanced glycation end products in ossified ligament tissues in vitro. Spine 32(11):E337–E339CrossRef

Chen Y, Wang X, Yang H, Miao J, Liu X, Chen D (2014) Upregulated expression of perk in spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament. Eur Spine J 23:447–454CrossRef

10.

Inamasu J, Guiot BH, Sachs DC (2006) Ossification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history. Neurosurgery 58(6):1027–1039CrossRef

11.

Kato Y, Kanchiku T, Imajo Y et al (2010) Biomechanical study of the effect of degree of static compression of the spinal cord in ossification of the posterior longitudinal ligament. J Neurosurg Spine 12(3):301–305CrossRef

12.

Tsukamoto N, Maeda T, Miura H et al (2006) Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine 5(3):234–242CrossRef

13.

Iwasawa T, Iwasaki K, Sawada T et al (2006) Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int 79(6):422–430CrossRef

14.

Iwasaki K, Furukawa KI, Tanno M et al (2004) Uniaxial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int 74(5):448–457CrossRef

15.

Yang HS, Lu XH, Chen DY, Yuan W, Yang LL, Chen Y, He HL (2011) Mechanical strain induces Cx43 expression in spinal ligament fibroblasts derived from patients presenting ossification of the posterior longitudinal ligament. Eur Spine J 20:1459–1465CrossRef

16.

Cheng WP, Wu GJ, Wang BW, Shyu KG (2012) Regulation of PUMA induced by mechanical stress in rat cardiomyocytes. J Biomed Sci 19:72CrossRef

17.

Cheng WP, Wu GJ, Wang BW, Shyu KG (2008) The molecular regulation of GADD153 in apoptosis of cultured vascular smooth muscle cells by cyclic mechanical stretch. Cardiovasc Res 77(3):551–559CrossRef

18.

Davies PF, Civelek M (2011) Endoplasmic reticulum stress, redox, and proinflammatory environment in athero-susceptible endothelium in vivo at sites of complex hemodynamic shear stress. Antioxid Redox Signal 15(5):1427–1432CrossRef

19.

Zhang YH, Zhao CQ, Jiang LS, Dai LY (2011) Cyclic stretch-induced apoptosis in rate annulus fibrosus cells is mediated in part by endoplasmic reticulum stress through nitric oxide production. Eur Spine J 20(8):1233–1243CrossRef

20.

Yang Shuang-Yan, Wei Fu-Lan, Li-Hua Hu, Wang Chun-Ling (2016) PERK-eIF2α-ATF4 pathway mediated by endoplasmic reticulum stress response is involved in osteodifferentiation of human periodontal ligament cells under cyclic mechanical force. Cell Signal 28(8):880–886CrossRef

21.

Chen D, Liu Y, Yang H, Chen D, Zhang X, Fermandes JC, Chen Y (2016) Connexin 43 promotes ossification of the posterior longitudinal ligament through activation of the erk1/2 and p38 mapk pathways. Cell Tissue Res 363:765–773CrossRef

22.

Jeong K, Oh Y, Kim S et al (2014) Apelin is transcriptionally regulate by ER stress-induced ATF4 expression via a p38 MAPK-dependent pathway. Apoptosis 19:1399–1410CrossRef

23.

Olivares S, Green RM, Henkel AS (2014) Endoplasmic reticulum stress activates the hepatic activator protein 1 complex via mitogen activated protein kinase-dependent signaling pathways. PLoS ONE 9(7):e103828CrossRef

24.

Krupkova O, Sadowska A, Kameda T et al (2018) p38 MAPK Facilitates crosstalk between endoplasmic reticulum stress and IL-6 release in the intervertebral disc. Front Immunol 9:1706CrossRef

25.

Ayala P, Montenegro J, Vivar R et al (2012) Attenuation of endoplasmic reticulum stress using the chemical chaperone 4-phenylbutyric acid prevents cardiac fibrosis induced by isoproterenol. Exp Mol Pathol 92(1):97–104CrossRef

26.

Wei J, Sheng X, Feng D et al (2008) PERK is essential for neonatal skeletal development to regulate osteoblast proliferation and differentiation. J Cell Physiol 217(3):693–707CrossRef

27.

Saito A, Ochiai K, Kondo S et al (2011) Endoplasmic reticulum stress response mediated by the PERK-elF2a-ATF4 pathway is involved in osteoblast differentiation induced by BMP2. J Biol Chem 286(6):4809–4818CrossRef

28.

Brickwood S, Bonthron DT, AI-Gazali LI et al (2003) Wolcott-Rallison syndrome: pathogenicinsights into neonatal diabetes from new mutation and expression studies of EIF2AK3. J Med Genet 40(9):685–689CrossRef

Titel: Endoplasmic reticulum stress regulates mechanical stress-induced ossification of posterior longitudinal ligament
verfasst von: Lei Shi
Jinhao Miao
Deyu Chen
Jiangang Shi
Yu Chen
Publikationsdatum: 19.07.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: European Spine Journal / Ausgabe 10/2019
Print ISSN: 0940-6719
Elektronische ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-019-06074-2

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen.
» Jetzt entdecken

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Graphic abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2019

Clival screw and plate fixation by the transoral approach for the craniovertebral junction: a CT-based feasibility study

The most appropriate cervical vertebra for the measurement of occipitocervical inclination parameter: a validation study of C3, C4, and C5 levels using multi-positional magnetic resonance imaging

Comparison of a novel anterior-only approach and the conventional posterior–anterior approach for cervical facet dislocation: a retrospective study

Announcements

Risk assessment of vertebral artery injury in anterior controllable antedisplacement and fusion (ACAF) surgery: a cadaveric and radiologic study