One strike loading organ culture model to investigate the post-traumatic disc degenerative condition.

Degeneration Extracellular matrix Intervertebral disc Mechanical injury One strike loading Post-traumatic

Journal

Journal of orthopaedic translation
ISSN: 2214-031X
Titre abrégé: J Orthop Translat
Pays: Singapore
ID NLM: 101625127

Informations de publication

Date de publication:
Jan 2021
Historique:
received: 15 04 2020
revised: 01 07 2020
accepted: 09 08 2020
entrez: 13 1 2021
pubmed: 14 1 2021
medline: 14 1 2021
Statut: epublish

Résumé

Acute trauma on intervertebral discs (IVDs) is thought to be one of the risk factors for IVD degeneration. The pathophysiology of IVD degeneration induced by single high impact mechanical injury is not very well understood. The aim of this study was using a post-traumatic IVD model in a whole organ culture system to analyze the biological and biomechanical consequences of the single high-impact loading event on the cultured IVDs. Isolated healthy bovine IVDs were loaded with a physiological loading protocol in the control group or with injurious loading (compression at 50% of IVD height) in the one strike loading (OSL) group. After another 1 day (short term) or 8 days (long term) of whole organ culture within a bioreactor, the samples were collected to analyze the cell viability, histological morphology and gene expression. The conditioned medium was collected daily to analyze the release of glycosaminoglycan (GAG) and nitric oxide (NO). The OSL IVD injury group showed signs of early degeneration including reduction of dynamic compressive stiffness, annulus fibrosus (AF) fissures and extracellular matrix degradation. Compared to the control group, the OSL model group showed more severe cell death (P ​< ​0.01) and higher GAG release in the culture medium (P ​< ​0.05). The MMP and ADAMTS families were up-regulated in both nucleus pulposus (NP) and AF tissues from the OSL model group (P ​< ​0.05). The OSL injury model induced a traumatic degenerative cascade in the whole organ cultured IVD. The present study shows a single hyperphysiological mechanical compression applied to healthy bovine IVDs caused significant drop of cell viability, altered the mRNA expression in the IVD, and increased ECM degradation. The OSL IVD model could provide new insights into the mechanism of mechanical injury induced early IVD degeneration. This model has a high potential for investigation of the degeneration mechanism in post-traumatic IVD disease, identification of novel biomarkers and therapeutic targets, as well as screening of treatment therapies.

Sections du résumé

BACKGROUND BACKGROUND
Acute trauma on intervertebral discs (IVDs) is thought to be one of the risk factors for IVD degeneration. The pathophysiology of IVD degeneration induced by single high impact mechanical injury is not very well understood. The aim of this study was using a post-traumatic IVD model in a whole organ culture system to analyze the biological and biomechanical consequences of the single high-impact loading event on the cultured IVDs.
METHODS METHODS
Isolated healthy bovine IVDs were loaded with a physiological loading protocol in the control group or with injurious loading (compression at 50% of IVD height) in the one strike loading (OSL) group. After another 1 day (short term) or 8 days (long term) of whole organ culture within a bioreactor, the samples were collected to analyze the cell viability, histological morphology and gene expression. The conditioned medium was collected daily to analyze the release of glycosaminoglycan (GAG) and nitric oxide (NO).
RESULTS RESULTS
The OSL IVD injury group showed signs of early degeneration including reduction of dynamic compressive stiffness, annulus fibrosus (AF) fissures and extracellular matrix degradation. Compared to the control group, the OSL model group showed more severe cell death (P ​< ​0.01) and higher GAG release in the culture medium (P ​< ​0.05). The MMP and ADAMTS families were up-regulated in both nucleus pulposus (NP) and AF tissues from the OSL model group (P ​< ​0.05). The OSL injury model induced a traumatic degenerative cascade in the whole organ cultured IVD.
CONCLUSIONS CONCLUSIONS
The present study shows a single hyperphysiological mechanical compression applied to healthy bovine IVDs caused significant drop of cell viability, altered the mRNA expression in the IVD, and increased ECM degradation. The OSL IVD model could provide new insights into the mechanism of mechanical injury induced early IVD degeneration.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE UNASSIGNED
This model has a high potential for investigation of the degeneration mechanism in post-traumatic IVD disease, identification of novel biomarkers and therapeutic targets, as well as screening of treatment therapies.

Identifiants

pubmed: 33437633
doi: 10.1016/j.jot.2020.08.003
pii: S2214-031X(20)30097-8
pmc: PMC7773974
doi:

Types de publication

Journal Article

Langues

eng

Pagination

141-150

Informations de copyright

© 2020 The Authors.

Déclaration de conflit d'intérêts

The authors have no conflicts of interest to disclose in relation to this article.

Références

JOR Spine. 2018 Sep;1(3):
pubmed: 30569032
Biomaterials. 2016 Apr;84:196-209
pubmed: 26828684
Spine (Phila Pa 1976). 2009 Jan 15;34(2):131-40
pubmed: 19139663
Eur Spine J. 2012 Aug;21 Suppl 6:S810-8
pubmed: 21837413
Connect Tissue Res. 2020 May-Jul;61(3-4):304-321
pubmed: 31556329
PLoS One. 2013 Apr 30;8(4):e62411
pubmed: 23638074
J Bone Joint Surg Am. 1981 Jul;63(6):891-9
pubmed: 6453878
Eur Radiol. 2006 Nov;16(11):2533-41
pubmed: 16775692
Spine J. 2013 Mar;13(3):235-42
pubmed: 23537452
Biochim Biophys Acta. 1986 Sep 4;883(2):173-7
pubmed: 3091074
Eur Spine J. 2015 Sep;24(9):1901-8
pubmed: 24736931
Spine (Phila Pa 1976). 1983 Nov-Dec;8(8):817-31
pubmed: 6670016
J Orthop Res. 2017 Jan;35(1):51-60
pubmed: 27340938
Spine (Phila Pa 1976). 2006 Dec 15;31(26):3052-60
pubmed: 17173003
Eur Spine J. 2008 Feb;17(2):289-99
pubmed: 17929064
Biomed Res Int. 2016;2016:5952165
pubmed: 27314030
Spine (Phila Pa 1976). 2000 Feb 15;25(4):487-92
pubmed: 10707396
JOR Spine. 2019 Mar 22;2(1):e1047
pubmed: 31463461
Spine (Phila Pa 1976). 2015 Dec;40(23):1799-806
pubmed: 26571062
Histol Histopathol. 2018 Jun;33(6):543-554
pubmed: 28580566
Global Spine J. 2013 Jun;3(3):145-52
pubmed: 24436865
JOR Spine. 2018 Sep;1(3):
pubmed: 30687810
Regen Med. 2014 May;9(3):309-26
pubmed: 24935043
Clin Anat. 2015 Mar;28(2):195-204
pubmed: 24753325
Spine (Phila Pa 1976). 1994 Apr 15;19(8):935-40
pubmed: 8009352
Eur Spine J. 2016 Sep;25(9):2898-908
pubmed: 27037921
Spine (Phila Pa 1976). 2000 Jul 1;25(13):1625-36
pubmed: 10870137
Spine (Phila Pa 1976). 1990 May;15(5):402-10
pubmed: 2363068
J Tissue Eng Regen Med. 2018 Apr;12(4):e2051-e2061
pubmed: 29320615
J Anat. 2012 Dec;221(6):480-96
pubmed: 22686699
JOR Spine. 2018 Sep;1(3):e1029
pubmed: 30895276
Eur Cell Mater. 2014 Sep 12;28:98-110; discussion 110-1
pubmed: 25214017
Orthop Clin North Am. 2011 Oct;42(4):447-64, vii
pubmed: 21944583
J Clin Invest. 1996 Aug 15;98(4):996-1003
pubmed: 8770872
Eur J Health Econ. 2011 Oct;12(5):455-67
pubmed: 20526649
JOR Spine. 2018 May 23;1(2):e1015
pubmed: 31463442
Osteoarthritis Cartilage. 2015 Jul;23(7):1057-70
pubmed: 25827971
Lancet. 2012 Dec 15;380(9859):2071-94
pubmed: 23245603
JOR Spine. 2018 Dec;1(4):e1036
pubmed: 30895277
Int J Mol Sci. 2017 May 12;18(5):
pubmed: 28498326
Orthop Clin North Am. 2011 Oct;42(4):487-99, vii
pubmed: 21944586
Matrix Biol. 2009 Sep;28(7):384-9
pubmed: 19586615
JOR Spine. 2018 Mar 15;1(1):e1005
pubmed: 31463437
J Biomech. 2005 Mar;38(3):557-65
pubmed: 15652555
Eur Spine J. 2008 Jan;17(1):2-19
pubmed: 17632738
Osteoarthritis Cartilage. 2011 Aug;19(8):1011-8
pubmed: 21549847
J Biomech. 2014 Sep 22;47(12):2983-8
pubmed: 25085756
Spine (Phila Pa 1976). 2011 Dec 15;36(26):2260-6
pubmed: 21228748
JOR Spine. 2019 Sep 02;2(3):e1065
pubmed: 31572982
JOR Spine. 2018 Jun 19;1(2):e1017
pubmed: 31463444

Auteurs

Zhiyu Zhou (Z)

The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
AO Research Institute Davos, Davos, Switzerland.
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Shangbin Cui (S)

AO Research Institute Davos, Davos, Switzerland.
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Jie Du (J)

AO Research Institute Davos, Davos, Switzerland.

R Geoff Richards (RG)

AO Research Institute Davos, Davos, Switzerland.
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Mauro Alini (M)

AO Research Institute Davos, Davos, Switzerland.

Sibylle Grad (S)

AO Research Institute Davos, Davos, Switzerland.

Zhen Li (Z)

AO Research Institute Davos, Davos, Switzerland.

Classifications MeSH