Prostaglandin E2 induces dual-specificity phosphatase-1, thereby attenuating inflammatory genes expression in human osteoarthritic synovial fibroblasts

Asato Maekawa; Yasunobu Sawaji; Kenji Endo; Takuya Kusakabe; Takamitsu Konishi; Toshiyuki Tateiwa; Toshinori Masaoka; Takaaki Shishido; Kengo Yamamoto

doi:10.1016/j.prostaglandins.2021.106550

Prostaglandin E₂ induces dual-specificity phosphatase-1, thereby attenuating inflammatory genes expression in human osteoarthritic synovial fibroblasts

Prostaglandins Other Lipid Mediat. 2021 Jun:154:106550. doi: 10.1016/j.prostaglandins.2021.106550. Epub 2021 Apr 18.

Authors

Asato Maekawa¹, Yasunobu Sawaji², Kenji Endo¹, Takuya Kusakabe¹, Takamitsu Konishi¹, Toshiyuki Tateiwa¹, Toshinori Masaoka¹, Takaaki Shishido¹, Kengo Yamamoto¹

Affiliations

¹ Department of Orthopedic Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
² Department of Orthopedic Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan. Electronic address: sawayasu@mac.com.

PMID: 33857603
DOI: 10.1016/j.prostaglandins.2021.106550

Abstract

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_2. The objective of this study was to clarify the suppressive mechanism of PGE₂ 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. PGE₂ 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 PGE₂ has novel biological activity that suppresses NGF and MMPs expression by inducing DUSP-1 expression.

Keywords: Inflammation; Matrix degeneration; Osteoarthritis; Pain; Prostaglandin E(2); Synovium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Interleukin-1beta*

Substances

IL1B protein, human
Interleukin-1beta