Prostaglandin E2 mediates sensory nerve regulation of bone homeostasis.
Adrenergic Fibers
/ drug effects
Adrenergic beta-Antagonists
/ pharmacology
Animals
Bone Density
/ drug effects
Bone Regeneration
/ drug effects
Bone and Bones
/ cytology
Cells, Cultured
Cyclooxygenase 2
/ genetics
Dinoprostone
/ metabolism
Disease Models, Animal
Feedback, Physiological
Female
Humans
Hydroxyprostaglandin Dehydrogenases
/ antagonists & inhibitors
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteoblasts
/ drug effects
Osteoporosis
/ etiology
Propranolol
/ pharmacology
Pyridines
/ pharmacology
Receptors, Prostaglandin E, EP4 Subtype
/ genetics
Sensory Receptor Cells
/ drug effects
Thiophenes
/ pharmacology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 01 2019
14 01 2019
Historique:
received:
25
03
2018
accepted:
14
12
2018
entrez:
16
1
2019
pubmed:
16
1
2019
medline:
20
2
2019
Statut:
epublish
Résumé
Whether sensory nerve can sense bone density or metabolic activity to control bone homeostasis is unknown. Here we found prostaglandin E2 (PGE2) secreted by osteoblastic cells activates PGE2 receptor 4 (EP4) in sensory nerves to regulate bone formation by inhibiting sympathetic activity through the central nervous system. PGE2 secreted by osteoblasts increases when bone density decreases as demonstrated in osteoporotic animal models. Ablation of sensory nerves erodes the skeletal integrity. Specifically, knockout of the EP4 gene in the sensory nerves or cyclooxygenase-2 (COX2) in the osteoblastic cells significantly reduces bone volume in adult mice. Sympathetic tone is increased in sensory denervation models, and propranolol, a β2-adrenergic antagonist, rescues bone loss. Furthermore, injection of SW033291, a small molecule to increase PGE2 level locally, significantly boostes bone formation, whereas the effect is obstructed in EP4 knockout mice. Thus, we show that PGE2 mediates sensory nerve to control bone homeostasis and promote regeneration.
Identifiants
pubmed: 30643142
doi: 10.1038/s41467-018-08097-7
pii: 10.1038/s41467-018-08097-7
pmc: PMC6331599
doi:
Substances chimiques
Adrenergic beta-Antagonists
0
Ptger4 protein, mouse
0
Pyridines
0
Receptors, Prostaglandin E, EP4 Subtype
0
SW033291
0
Thiophenes
0
Propranolol
9Y8NXQ24VQ
Hydroxyprostaglandin Dehydrogenases
EC 1.1.1.-
15-hydroxyprostaglandin dehydrogenase
EC 1.1.1.141
Ptgs2 protein, mouse
EC 1.14.99.-
Cyclooxygenase 2
EC 1.14.99.1
Dinoprostone
K7Q1JQR04M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
181Commentaires et corrections
Type : CommentIn
Références
Drugs Today (Barc). 2008 Sep;44(9):693-709
pubmed: 19137124
Endocrinology. 2005 Jan;146(1):503-10
pubmed: 15498888
Nat Med. 2014 Nov;20(11):1270-8
pubmed: 25282358
J Comp Neurol. 1999 Dec 20;415(3):341-67
pubmed: 10553119
BMC Gastroenterol. 2014 Nov 25;14:202
pubmed: 25421900
Neurosci Lett. 1987 May 6;76(2):151-6
pubmed: 2438603
J Clin Invest. 1996 Dec 1;98(11):2446-9
pubmed: 8958205
Bone. 1999 Dec;25(6):623-9
pubmed: 10593406
Cell. 2009 Sep 4;138(5):976-89
pubmed: 19737523
Rheumatol Int. 2009 Nov;30(1):39-43
pubmed: 19306095
Prostaglandins Other Lipid Mediat. 2003 Jul;71(3-4):287-92
pubmed: 14518568
Nat Med. 2002 Feb;8(2):91-2
pubmed: 11821873
Sci Transl Med. 2017 May 10;9(389):
pubmed: 28490668
J Neurosci. 1991 Mar;11(3):852-68
pubmed: 1705972
Nat Genet. 2008 Jun;40(6):789-93
pubmed: 18500342
Trends Pharmacol Sci. 1998 Apr;19(4):141-7
pubmed: 9612089
Nat Med. 2016 Oct;22(10):1170-1179
pubmed: 27595322
Inflamm Allergy Drug Targets. 2009 Jul;8(3):169-75
pubmed: 19601876
Cell. 2000 Jan 21;100(2):197-207
pubmed: 10660043
Prostaglandins Leukot Essent Fatty Acids. 2005 Dec;73(6):423-30
pubmed: 16198098
Biol Pharm Bull. 2011;34(8):1170-3
pubmed: 21804201
J Cell Biochem. 2006 Oct 15;99(3):845-52
pubmed: 16721830
Arch Biochem Biophys. 1989 May 1;270(2):588-95
pubmed: 2495768
Ann N Y Acad Sci. 1990;604:222-36
pubmed: 1977349
Rev Endocr Metab Disord. 2016 Jun;17(2):149-58
pubmed: 27511471
Nat Protoc. 2008;3(7):1167-70
pubmed: 18600221
Nature. 2013 May 23;497(7450):490-3
pubmed: 23644455
Nature. 2014 Mar 20;507(7492):323-328
pubmed: 24646994
Bone. 1996 Jan;18(1):29-39
pubmed: 8717534
Case Rep Pediatr. 2015;2015:589852
pubmed: 26579324
Anat Rec A Discov Mol Cell Evol Biol. 2004 Sep;280(1):827-35
pubmed: 15382018
Genes Dev. 2010 Oct 15;24(20):2330-42
pubmed: 20952540
Trends Endocrinol Metab. 2010 May;21(5):294-301
pubmed: 20079660
J Mol Endocrinol. 2010 Oct;45(4):175-81
pubmed: 20660619
Nat Med. 2010 Nov;16(11):1258-66
pubmed: 20948531
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4580-5
pubmed: 11917107
Trends Immunol. 2017 Jan;38(1):5-19
pubmed: 27793571
Eur J Neurosci. 1991;3(3):249-259
pubmed: 12106203
Tissue Eng. 2005 Nov-Dec;11(11-12):1832-9
pubmed: 16411829
J Musculoskelet Neuronal Interact. 2004 Jun;4(2):132-4
pubmed: 15615111
Neuroscience. 2002;113(1):155-66
pubmed: 12123694
Science. 2017 Dec 1;358(6367):
pubmed: 29191879
Bone. 2018 Oct;115:2-7
pubmed: 28843700
J Bone Miner Res. 2006 Nov;21(11):1803-10
pubmed: 17002569
Bone. 2009 Jun;44(6):1177-85
pubmed: 19233324
Bone. 2009 Jul;45(1):98-103
pubmed: 19344793
Curr Pain Headache Rep. 2001 Feb;5(1):20-6
pubmed: 11252134
J Biol Chem. 2005 Aug 26;280(34):30192-200
pubmed: 15961387
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12098-102
pubmed: 16880406
Am J Physiol Endocrinol Metab. 2003 Sep;285(3):E608-13
pubmed: 12746215
Spinal Cord. 2002 Jul;40(7):313-26
pubmed: 12080459
Bone. 2018 Oct;115:8-14
pubmed: 28863948
Science. 2015 Jun 12;348(6240):aaa2340
pubmed: 26068857
J Bone Joint Surg Br. 2002 Mar;84(2):252-7
pubmed: 11922368