Nepetin inhibits osteoclastogenesis by inhibiting RANKL-induced activation of NF-κB and MAPK signalling pathway, and autophagy.
Animals
Autophagy
/ drug effects
Biomarkers
Bone Resorption
/ diagnostic imaging
Cell Line
Cell Survival
/ drug effects
Flavones
/ pharmacology
Immunohistochemistry
Male
Mice
Mitogen-Activated Protein Kinases
/ metabolism
NF-kappa B
/ metabolism
Osteogenesis
/ drug effects
Osteolysis
Signal Transduction
/ drug effects
X-Ray Microtomography
TRAF6
bone destruction
nepetin
osteoclasts
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
06
01
2020
revised:
20
09
2020
accepted:
15
10
2020
pubmed:
3
11
2020
medline:
20
5
2021
entrez:
2
11
2020
Statut:
ppublish
Résumé
Aseptic prosthetic loosening due to wear particle-induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro-osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extensive bone destruction around the bone-implant interface. Here we showed that Nepetin, a natural bioactive flavonoid with proven anti-inflammatory and anti-proliferative properties, potently inhibited RANKL-induced osteoclast differentiation, formation and bone resorption in vitro, and protected mice against the deleterious effects of titanium particle-induced calvarial osteolysis in vivo. Mechanistically, Nepetin attenuated RANKL-induced activation of NF-κB and MAPK signalling pathways and TRAF6-dependent ubiquitination of Beclin 1 which is necessary for the induction of autophagy. In brief, our study demonstrates the potential therapeutic application of Nepetin against osteoclast-mediated osteolytic diseases.
Identifiants
pubmed: 33135301
doi: 10.1111/jcmm.16055
pmc: PMC7754000
doi:
Substances chimiques
Biomarkers
0
Flavones
0
NF-kappa B
0
Mitogen-Activated Protein Kinases
EC 2.7.11.24
eupafolin
I3O7LF3GED
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14366-14380Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Science. 2019 Nov 15;366(6467):818-822
pubmed: 31727826
J Cell Mol Med. 2020 Dec;24(24):14366-14380
pubmed: 33135301
J Biol Chem. 2002 Nov 15;277(46):44347-56
pubmed: 12185073
Gene Ther. 2004 Feb;11(4):402-7
pubmed: 14724679
Can J Surg. 2012 Dec;55(6):408-17
pubmed: 22992398
Nature. 2019 Apr;568(7753):541-545
pubmed: 30971820
J Cell Physiol. 2019 Dec;234(12):22960-22971
pubmed: 31127627
BMC Complement Altern Med. 2019 Oct 15;19(1):269
pubmed: 31615565
Pharmazie. 2004 Dec;59(12):965-6
pubmed: 15638088
J Clin Invest. 2014 Jan;124(1):297-310
pubmed: 24316970
Apoptosis. 2019 Feb;24(1-2):3-20
pubmed: 30288639
J Mater Chem B. 2014 Nov 7;2(41):7094-7108
pubmed: 25541591
Front Immunol. 2019 Jun 19;10:1408
pubmed: 31275328
J Exp Med. 1999 Dec 20;190(12):1741-54
pubmed: 10601350
Arthritis Res Ther. 2007;9 Suppl 1:S6
pubmed: 17634145
J Bone Miner Res. 2019 Sep;34(9):1753-1766
pubmed: 31074883
Bone. 2019 Jul;124:69-74
pubmed: 30959190
Int J Biochem Cell Biol. 2014 Sep;54:198-207
pubmed: 25091703
Nat Rev Mol Cell Biol. 2020 Feb;21(2):101-118
pubmed: 31768005
Pediatr Endocrinol Rev. 2019 Dec;17(2):84-99
pubmed: 31763801
Genes Dev. 1999 Apr 15;13(8):1015-24
pubmed: 10215628
Mol Cells. 2017 Oct;40(10):706-713
pubmed: 29047262
Front Pharmacol. 2019 Oct 22;10:1248
pubmed: 31708778
Biomed Pharmacother. 2017 Jan;85:704-711
pubmed: 27923689
J Bone Miner Res. 2020 Feb;35(2):239-247
pubmed: 31589776
Autophagy. 2013 Aug;9(8):1253-5
pubmed: 23811580
Bone Res. 2019 Oct 3;7:28
pubmed: 31666998
J Cell Physiol. 2019 Aug;234(8):12105-12115
pubmed: 30820954
Front Immunol. 2018 Dec 18;9:2963
pubmed: 30619321
J Clin Med. 2019 Dec 01;8(12):
pubmed: 31805704
Hawaii J Health Soc Welf. 2019 Nov;78(11 Suppl 2):47-51
pubmed: 31773111
Mol Carcinog. 2015 Sep;54(9):751-60
pubmed: 24700667
J Clin Med. 2019 Jun 28;8(7):
pubmed: 31261703
J Ethnopharmacol. 2011 Sep 1;137(1):371-81
pubmed: 21669270
Dev Cell. 2011 Nov 15;21(5):966-74
pubmed: 22055344
Stem Cells Int. 2019 Jul 1;2019:5214501
pubmed: 31354840
Lancet. 2018 Nov 3;392(10158):1672-1682
pubmed: 30496082
IUBMB Life. 2005 Jun;57(6):389-95
pubmed: 16012047
J Biol Chem. 2007 Jun 22;282(25):18245-18253
pubmed: 17485464
Clin Orthop Relat Res. 2007 Jan;454:251-61
pubmed: 16980902
Microbiol Spectr. 2016 Jun;4(3):
pubmed: 27337470