Extracellular adenosine 5ʹ-diphosphate promotes MCP-1/CCL2 expression via the P2Y13 purinergic receptor/ERK signaling axis in temporomandibular joint-derived mouse fibroblast-like synoviocytes

Background Temporomandibular joint osteoarthritis (TMJ-OA) causes cartilage degeneration, bone cavitation, and fibrosis of the TMJ. However, the mechanisms underlying the fibroblast-like synoviocyte (FLS)-mediated inflammatory activity in TMJ-OA remain unclear. Methods and results Reverse transcript...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology reports 2023-02, Vol.50 (2), p.1595-1602
Main Authors: Yokota, Seiji, Chosa, Naoyuki, Matsumoto, Shikino, Satoh, Kazuro, Ishisaki, Akira
Format: Article
Language:English
Subjects:
Adenosine
Agonists
Animal Anatomy
Animal Biochemistry
Biomedical and Life Sciences
Cartilage diseases
Cavitation
Chemokines
Degeneration
Extracellular signal-regulated kinase
Fibroblasts
Fibrosis
Histology
Inflammation
Kinases
Life Sciences
MAP kinase
Monocyte chemoattractant protein 1
Monocytes
Morphology
Original
Original Article
Osteoarthritis
Phosphorylation
Reverse transcription
Signal transduction
Synoviocytes
Temporomandibular joint
Therapeutic targets
Uracil
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background Temporomandibular joint osteoarthritis (TMJ-OA) causes cartilage degeneration, bone cavitation, and fibrosis of the TMJ. However, the mechanisms underlying the fibroblast-like synoviocyte (FLS)-mediated inflammatory activity in TMJ-OA remain unclear. Methods and results Reverse transcription-quantitative polymerase chain reaction analysis revealed that the P2Y 1 , P2Y 12 , and P2Y 13 purinergic receptor agonist adenosine 5ʹ-diphosphate (ADP) significantly induces monocyte chemotactic protein 1 (MCP-1)/ C–C motif chemokine ligand 2 (CCL2) expression in the FLS1 synovial cell line. In contrast, the uracil nucleotide UTP, which is a P2Y 2 and P2Y 4 agonist, has no significant effect on MCP-1/CCL2 production in FLS1 cells. In addition, the P2Y 13 antagonist MRS 2211 considerably decreases the expression of ADP-induced MCP-1/CCL2, whereas ADP stimulation enhances extracellular signal-regulated kinase (ERK) phosphorylation. Moreover, it was found that the mitogen-activated protein kinase/ERK kinase (MEK) inhibitor U0126 reduces ADP-induced MCP-1/CCL2 expression. Conclusion ADP enhances MCP-1/CCL2 expression in TMJ FLSs via P2Y 13 receptors in an MEK/ERK-dependent manner, thus resulting in inflammatory cell infiltration in the TMJ. Collectively, the findings of this study contribute to a partial clarification of the signaling pathway underlying the development of inflammation in TMJ-OA and can help identify potential therapeutic targets for suppressing ADP-mediated purinergic signaling in this disease.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-022-08125-2