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.

骨关节炎 (OA) 的特征是关节疼痛和软骨退化。变性是由基质金属蛋白酶 (MMP) 的过度诱导引起的，疼痛是由神经生长因子 (NGF) 依赖的神经侵入滑膜组织引起的，以及前列腺素 (PG)E 引起的伤害性疼痛_2.本研究的目的旨在通过关注人滑膜成纤维细胞中的丝裂原活化蛋白激酶 (MAPKs) 及其内源性磷酸酶、双特异性磷酸酶 (DUSP)-1来阐明 PGE _{2对 MMP 和 NGF 调节的抑制机制。}PGE ₂强烈增加 DUSP-1 并抑制 IL-1β 诱导的 MAPKs 磷酸化。选择性抑制剂对 MAPKs 的抑制差异调节 IL-1β 诱导的 MMPs 表达和 NGF 表达。IL-1β诱导的MAPKs磷酸化在DUSP-1敲低细胞中延长和增强，MMPs和NGF的表达也增加。该研究表明，PGE ₂具有新的生物活性，可通过诱导 DUSP-1 表达来抑制 NGF 和 MMPs 的表达。