Prostaglandin E 2 induces dual-specificity phosphatase-1, thereby attenuating inflammatory genes expression in human osteoarthritic synovial fibroblasts

• Published in: Prostaglandins & other lipid mediators Vol. 154; p. 106550
• Main Authors: Maekawa, Asato, Sawaji, Yasunobu, Endo, Kenji, Kusakabe, Takuya, Konishi, Takamitsu, Tateiwa, Toshiyuki, Masaoka, Toshinori, Shishido, Takaaki, Yamamoto, Kengo
• Format: Journal Article
• Language: English
• Published: United States 01-06-2021
• Subjects: Cells, Cultured; Dinoprostone - metabolism; Dual Specificity Phosphatase 1 - genetics; Dual Specificity Phosphatase 1 - metabolism; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation - drug effects; Humans; Interleukin-1beta - metabolism; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Nerve Growth Factor - genetics; Nerve Growth Factor - metabolism; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Phosphorylation - drug effects; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; Pain; Matrix degeneration; Inflammation; Prostaglandin E; Osteoarthritis; Synovium
• ISSN: 1098-8823

Characteristic features of osteoarthritis (OA) are joint pain and cartilage degeneration. The degeneration is caused by excess induction of matrix metalloproteinases (MMPs) and the pain is caused by nerve growth factor (NGF)-dependent nerve invasion into synovial tissue in addition to nociceptive pain by prostaglandin (PG)E
The objective of this study was to clarify the suppressive mechanism of PGE
on the regulation of MMPs and NGF by focusing on mitogen-activated protein kinases (MAPKs) and their endogenous phosphatase, dual-specificity phosphatase (DUSP)-1 in human synovial fibroblasts. PGE
strongly increased DUSP-1 and suppressed IL-1β-induced MAPKs phosphorylation. Inhibition of MAPKs by selective inhibitors differentially regulated the IL-1β-induced expression of MMPs and NGF expression. IL-1β-induced MAPKs phosphorylation was prolonged and enhanced in DUSP-1 knockdown cells and the expression of MMPs and NGF was also increased. This study revealed that PGE
has novel biological activity that suppresses NGF and MMPs expression by inducing DUSP-1 expression.