Department of Orthopaedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.
Department of Pain, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
Aging (Albany NY). 2020 Dec 15;12(24):26029-26046. doi: 10.18632/aging.202252.
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by deterioration of articular cartilage. Dual specificity phosphatase 5 (DUSP5), a member of the DUSP subfamily, is known to regulate cellular inflammation. Here, we studied the relationship between DUSP5 and OA by knockdown and overexpression DUSP5, respectively. Results from experiments demonstrated that the knockdown of DUSP5 increased interleukin-1β (IL-1β)-induced expression of inflammatory genes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), and matrix metalloproteinases (MMPs) in chondrocytes, whereas it decreased the expression of anti-inflammatory genes, such as tissue inhibitor of metalloproteinase 3 (TIMP3) and IL-10. Conversely, the overexpression of DUSP5 suppressed the IL-1β-induced expression of iNOS, COX-2, and MMPs, and upregulated the expression of TIMP3 and IL-10. Moreover, knockdown of DUSP5 enhanced the IL-1β-induced activation of NF-κB and ERK pathways, whereas its overexpression inhibited these pathways. DUSP5 overexpression prevented cartilage degeneration in a rat OA model, while its knockdown reversed that effect. Our findings reveal that DUSP5 suppresses IL-1β-induced chondrocyte inflammation by inhibiting the NF-κB and ERK signaling pathways and ameliorates OA.
骨关节炎（OA）是一种慢性退行性关节疾病，其特征为关节软骨恶化。双特异性磷酸酶 5（DUSP5）是 DUSP 亚家族的成员，已知其可调节细胞炎症。在这里，我们通过分别敲低和过表达 DUSP5 来研究 DUSP5 与 OA 之间的关系。实验结果表明，敲低 DUSP5 增加了白细胞介素-1β（IL-1β）诱导的软骨细胞中炎症基因的表达，如诱导型一氧化氮合酶（iNOS）、环氧化酶 2（COX2）和基质金属蛋白酶（MMPs），而降低了抗炎基因的表达，如金属蛋白酶组织抑制剂 3（TIMP3）和 IL-10。相反，过表达 DUSP5 抑制了 IL-1β诱导的 iNOS、COX-2 和 MMPs 的表达，并上调了 TIMP3 和 IL-10 的表达。此外，敲低 DUSP5 增强了 IL-1β诱导的 NF-κB 和 ERK 信号通路的激活，而过表达则抑制了这些通路。DUSP5 的过表达可预防大鼠 OA 模型中的软骨退化，而过表达则逆转了这一作用。我们的研究结果表明，DUSP5 通过抑制 NF-κB 和 ERK 信号通路抑制 IL-1β诱导的软骨细胞炎症，从而改善 OA。
