PMID- 36526849 OWN - NLM STAT- MEDLINE DCOM- 20230202 LR - 20230902 IS - 1573-4978 (Electronic) IS - 0301-4851 (Print) IS - 0301-4851 (Linking) VI - 50 IP - 2 DP - 2023 Feb TI - Extracellular adenosine 5'-diphosphate promotes MCP-1/CCL2 expression via the P2Y(13) purinergic receptor/ERK signaling axis in temporomandibular joint-derived mouse fibroblast-like synoviocytes. PG - 1595-1602 LID - 10.1007/s11033-022-08125-2 [doi] AB - 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 5'-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. CI - (c) 2022. The Author(s). FAU - Yokota, Seiji AU - Yokota S AUID- ORCID: 0000-0002-8576-3749 AD - Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 1-1-1 Idai-dori, Yahaba-cho, Shiwa-gun, 028-3694, Iwate, Japan. syokota@iwate-med.ac.jp. FAU - Chosa, Naoyuki AU - Chosa N AD - Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 1-1-1 Idai-dori, Yahaba-cho, Shiwa-gun, 028-3694, Iwate, Japan. FAU - Matsumoto, Shikino AU - Matsumoto S AD - Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University, 19-1 Uchimal, 020-8505, Morioka-shi, Iwate, Japan. FAU - Satoh, Kazuro AU - Satoh K AD - Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University, 19-1 Uchimal, 020-8505, Morioka-shi, Iwate, Japan. FAU - Ishisaki, Akira AU - Ishisaki A AD - Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, 1-1-1 Idai-dori, Yahaba-cho, Shiwa-gun, 028-3694, Iwate, Japan. aishisa@iwate-med.ac.jp. LA - eng GR - 19K19277/Japan Society for Promotion of Science/ PT - Journal Article DEP - 20221216 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (Chemokine CCL2) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - 0 (Diphosphates) RN - 0 (Ligands) RN - 0 (Receptors, Purinergic P2) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - K72T3FS567 (Adenosine) RN - 61D2G4IYVH (Adenosine Diphosphate) SB - IM MH - Mice MH - Animals MH - Chemokine CCL2/genetics/metabolism MH - Extracellular Signal-Regulated MAP Kinases MH - Diphosphates MH - *Synoviocytes/metabolism MH - Ligands MH - *Receptors, Purinergic P2/metabolism MH - Mitogen-Activated Protein Kinase Kinases MH - Temporomandibular Joint MH - Fibroblasts/metabolism MH - Adenosine MH - Adenosine Diphosphate/pharmacology/metabolism MH - Cells, Cultured PMC - PMC9889505 OTO - NOTNLM OT - Extracellular adenosine 5'-diphosphate OT - Extracellular signal-regulated kinase OT - Fibroblast-like synoviocytes OT - Monocyte chemotactic protein 1 OT - P2Y purinergic receptors OT - Temporomandibular joint COIS- The authors declare that they have no competing interests. EDAT- 2022/12/17 06:00 MHDA- 2023/02/03 06:00 PMCR- 2022/12/16 CRDT- 2022/12/16 23:38 PHST- 2022/06/13 00:00 [received] PHST- 2022/11/15 00:00 [accepted] PHST- 2022/12/17 06:00 [pubmed] PHST- 2023/02/03 06:00 [medline] PHST- 2022/12/16 23:38 [entrez] PHST- 2022/12/16 00:00 [pmc-release] AID - 10.1007/s11033-022-08125-2 [pii] AID - 8125 [pii] AID - 10.1007/s11033-022-08125-2 [doi] PST - ppublish SO - Mol Biol Rep. 2023 Feb;50(2):1595-1602. doi: 10.1007/s11033-022-08125-2. Epub 2022 Dec 16.