Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP.
Adenosine Triphosphate
/ analysis
Animals
Arthritis, Experimental
/ chemically induced
Bone Marrow Cells
/ cytology
Chemokine CXCL2
/ genetics
Chenodeoxycholic Acid
/ analogs & derivatives
Chronic Pain
/ etiology
Disease Models, Animal
Knee Joint
/ metabolism
Male
Mast Cells
/ cytology
Matrix Metalloproteinase 9
/ genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Oligopeptides
/ administration & dosage
Receptor, PAR-2
/ agonists
Receptors, Purinergic
/ metabolism
Synovial Fluid
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
19
01
2021
accepted:
18
05
2021
entrez:
4
6
2021
pubmed:
5
6
2021
medline:
18
11
2021
Statut:
epublish
Résumé
Conditions that resemble osteoarthritis (OA) were produced by injection of sodium monoiodoacetate (MIA) into the knee joints of mice. Bone marrow derived mast cells (BMMCs) injected into the OA knee joints enhanced spontaneous pain. Since no spontaneous pain was observed when BMMCs were injected into the knee joints of control mice that had not been treated with MIA, BMMCs should be activated within the OA knee joints and release some pain-inducible factors. Protease activated receptor-2 (PAR2) antagonist (FSLLRY-NH2) almost abolished the pain-enhancing effects of BMMCs injected into the OA knee joints, suggesting that tryptase, a mast cell protease that is capable of activating PAR2, should be released from the injected BMMCs and enhance pain through activation of PAR2. When PAR2 agonist (SLIGKV-NH2) instead of BMMCs was injected into the OA knee joints, it was also enhanced pain. Apyrase, an ATP degrading enzyme, injected into the OA knee joints before BMMCs suppressed the pain enhanced by BMMCs. We showed that purinoceptors (P2X4 and P2X7) were expressed in BMMCs and that extracellular ATP stimulated the release of tryptase from BMMCs. These observations suggest that ATP may stimulate degranulation of BMMCs and thereby enhanced pain. BMMCs injected into the OA knee joints stimulated expression of IL-1β, IL-6, TNF-α, CCL2, and MMP9 genes in the infrapatellar fat pads, and PAR2 antagonist suppressed the stimulatory effects of BMMCs. Our study suggests that intermittent pain frequently observed in OA knee joints may be due, at least partly, to mast cells through activation of PAR2 and action of ATP, and that intraarticular injection of BMMCs into the OA knee joints may provide a useful experimental system for investigating molecular mechanisms by which pain is induced in OA knee joints.
Identifiants
pubmed: 34086763
doi: 10.1371/journal.pone.0252590
pii: PONE-D-21-01925
pmc: PMC8177436
doi:
Substances chimiques
Chemokine CXCL2
0
F2rl1 protein, mouse
0
H-Phe-Ser-Leu-Leu-Arg-Tyr-NH2
0
Oligopeptides
0
Receptor, PAR-2
0
Receptors, Purinergic
0
seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide
0
Chenodeoxycholic Acid
0GEI24LG0J
3,7-dihydroxy-12-oxocholanoic acid
3MKE33N44O
Adenosine Triphosphate
8L70Q75FXE
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0252590Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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