The P2X7 purinergic receptor in intervertebral disc degeneration.
NLRP3
P2X7 receptor
inflammation
intervertebral disc degeneration
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
08
09
2021
received:
23
07
2021
accepted:
04
10
2021
pubmed:
21
10
2021
medline:
6
5
2022
entrez:
20
10
2021
Statut:
ppublish
Résumé
Mechanisms involved in the development of intervertebral disc (IVD) degeneration are only partially known, thus making the implementation of effective therapies very difficult. In this study, we investigated P2X7 purinergic receptor (P2X7R), NLRP3 inflammasome, and interleukin (IL)-1β expression in IVD specimens at different stages of disease progression, and during the in vitro dedifferentiation process of the primary cells derived thereof. We found that P2X7R, NLRP3, and IL-1β expression was higher in the IVD samples at a more advanced stage of degeneration and in the expanded IVD cells in culture which partially recapitulated the in vivo degeneration process. In IVD cells, the P2X7R showed a striking nuclear localization, while NLRP3 was mainly cytoplasmic. Stimulation with the semiselective P2X7R agonist benzoyl ATP together with lipopolysaccharide treatment triggered P2X7R transfer to the cytoplasm and P2X7R/NLRP3 colocalization. Taken together, these findings support pathophysiological evidence that the degenerated disc is a highly inflamed microenvironment and highlight the P2X7R/NLRP3 axis as a suitable therapeutic target. The immunohistochemical analysis and the assessment of subcellular localization revealed a substantial expression of P2X7R also in normal disc tissue. This gives us the opportunity to contribute to the few studies performed in natively expressed human P2X7R so far, and to understand the possible physiological ATP-mediated P2X7R homeostasis signaling. Therefore, collectively, our findings may offer a new perspective and pave the way for the exploration of a role of P2X7R-mediated purinergic signaling in IVD metabolism that goes beyond its involvement in inflammation.
Identifiants
pubmed: 34668208
doi: 10.1002/jcp.30611
pmc: PMC9298011
doi:
Substances chimiques
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
P2RX7 protein, human
0
Receptors, Purinergic P2X7
0
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1418-1428Informations de copyright
© 2021 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.
Références
Oncogene. 2017 Jan 19;36(3):293-303
pubmed: 27321181
Front Mol Neurosci. 2019 Aug 07;12:183
pubmed: 31440138
J Cell Physiol. 2021 Jan;236(1):641-652
pubmed: 32583512
Nat Rev Dis Primers. 2018 Dec 13;4(1):52
pubmed: 30546064
Purinergic Signal. 2009 Jun;5(2):163-73
pubmed: 19189228
Sci Rep. 2016 Oct 24;6:35804
pubmed: 27775097
Nat Cell Biol. 2018 Apr;20(4):373-381
pubmed: 29467443
Arthritis Rheum. 2010 Jul;62(7):1974-82
pubmed: 20222111
Cells. 2021 Jan 19;10(1):
pubmed: 33477845
Trends Cell Biol. 2018 May;28(5):392-404
pubmed: 29439897
Aging (Albany NY). 2018 Aug 20;10(8):2001-2015
pubmed: 30130742
Biochem Pharmacol. 2018 May;151:234-244
pubmed: 29288626
Am J Physiol Cell Physiol. 2020 May 1;318(5):C832-C835
pubmed: 32159362
JOR Spine. 2018 Sep;1(3):
pubmed: 30569032
Nature. 2002 Nov 7;420(6911):42
pubmed: 12422208
Semin Cell Dev Biol. 2020 May;101:123-139
pubmed: 31879265
Neurosurgery. 2017 Mar 01;80(3S):S46-S54
pubmed: 28350945
Methods Enzymol. 2019;629:115-150
pubmed: 31727237
Cell Mol Immunol. 2021 May;18(5):1141-1160
pubmed: 33850310
Semin Cell Dev Biol. 2017 Feb;62:94-103
pubmed: 27208724
Ageing Res Rev. 2007 Oct;6(3):247-61
pubmed: 17870673
Biochim Biophys Acta. 2013 Jul;1832(7):979-88
pubmed: 23562491
Function (Oxf). 2021 Jan 28;2(2):zqab005
pubmed: 35330818
Purinergic Signal. 2015 Dec;11(4):435-40
pubmed: 26318434
Osteoarthritis Cartilage. 2021 Jun;29(6):793-801
pubmed: 33609693
J Cell Physiol. 2019 Mar;234(3):2095-2103
pubmed: 30317598
Front Pharmacol. 2017 Mar 16;8:123
pubmed: 28360855
Auton Neurosci. 2003 Jul 31;106(2):103-9
pubmed: 12878079
Front Pharmacol. 2018 Feb 01;9:39
pubmed: 29449813
J Auton Nerv Syst. 2000 Jul 3;81(1-3):59-63
pubmed: 10869701
Signal Transduct Target Ther. 2021 Apr 28;6(1):162
pubmed: 33907179
Cancer Res. 2012 Jun 15;72(12):2957-69
pubmed: 22505653
FASEB J. 2015 Jun;29(6):2450-61
pubmed: 25690658
Curr Rev Musculoskelet Med. 2020 Dec;13(6):680-687
pubmed: 32705541
Clin Chim Acta. 2015 Oct 23;450:262-72
pubmed: 26341894
Int J Mol Sci. 2020 Nov 10;21(22):
pubmed: 33182829
Front Physiol. 2019 Jul 12;10:896
pubmed: 31354529
FASEB J. 2010 Sep;24(9):3393-404
pubmed: 20453110
Bone Res. 2020 Feb 13;8:7
pubmed: 32128275
Osteoarthritis Cartilage. 2015 Jul;23(7):1057-70
pubmed: 25827971
Respir Physiol Neurobiol. 2011 Dec 15;179(2-3):314-25
pubmed: 21982752
J Orthop Res. 2013 Nov;31(11):1733-8
pubmed: 23843186
Spine (Phila Pa 1976). 2001 Sep 1;26(17):1873-8
pubmed: 11568697
Immunity. 2017 Jul 18;47(1):15-31
pubmed: 28723547
Osteoarthritis Cartilage. 2019 Jan;27(1):41-48
pubmed: 30243946
Biomaterials. 2020 Sep;253:120107
pubmed: 32450408
Front Cell Dev Biol. 2021 Feb 11;9:628330
pubmed: 33644066
Nat Rev Rheumatol. 2019 Feb;15(2):102-112
pubmed: 30643232
Biotechnol Adv. 2018 Jan - Feb;36(1):281-294
pubmed: 29199133
Adv Pharmacol. 2011;61:333-72
pubmed: 21586364
Oxid Med Cell Longev. 2020 May 21;2020:7956274
pubmed: 32566102
J Cell Physiol. 2022 Feb;237(2):1418-1428
pubmed: 34668208
Cells Tissues Organs. 2019;207(3-4):165-176
pubmed: 31726456
Eur Cell Mater. 2017 Mar 24;33:240-251
pubmed: 28345732
Adv Drug Deliv Rev. 2019 Jun;146:306-324
pubmed: 29705378
Stem Cell Res Ther. 2021 Jan 7;12(1):34
pubmed: 33413668