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。退化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) 依赖性神经侵入滑膜组织引起的，此外还有前列腺素 (PG)E 造成的伤害性疼痛_2。本研究的目的旨在通过关注人滑膜成纤维细胞中丝裂原激活蛋白激酶（MAPK）及其内源性磷酸酶双特异性磷酸酶（DUSP）-1，阐明PGE ₂对MMPs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 MAPK 磷酸化。选择性抑制剂对 MAPK 的抑制可差异调节 IL-1β 诱导的 MMP 表达和 NGF 表达。在DUSP-1敲低细胞中，IL-1β诱导的MAPKs磷酸化时间延长并增强，MMPs和NGF的表达也增加。这项研究表明，PGE ₂具有新颖的生物活性，可通过诱导 DUSP-1 表达来抑制 NGF 和 MMP 的表达。