Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Int J Mol Med. 2019 May;43(5):2241-2251. doi: 10.3892/ijmm.2019.4141. Epub 2019 Mar 21.
Osteoarthritis (OA) is the most common type of degenerative joint disease and secreted inflammatory molecules serve a pivotal role in it. Peimine has been reported to have anti‑inflammatory activity. In order to investigate the potential therapeutic role of Peimine in OA, mouse articular chondrocytes were treated with IL‑1β and different doses of Peimine in vitro. The data revealed that Peimine not only suppressed IL‑1β‑induced production of nitric oxide (NO) and prostaglandin E2, but also reduced the protein levels of inducible NO synthase (iNOS) and cyclooxygenase‑2 (COX‑2). In addition, Peimine inhibited the IL‑1β‑induced mRNA expression of matrix metalloproteinase (MMP)‑1, MMP‑3, MMP‑9, MMP‑13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)‑4 and ADAMTS‑5. Furthermore, Peimine inhibited IL‑1β‑induced activation of the mitogen‑activated protein kinase (MAPK) pathway. The protective effect of Peimine on IL‑1β‑treated chondrocytes was attenuated following activation of the MAPK pathway, as demonstrated by the increased expression levels of MMP‑3, MMP‑13, ADAMTS‑5, iNOS and COX‑2 compared with the Peimine group. The in vivo data suggested that Peimine limited the development of OA in the mouse model. In general, the data indicate that Peimine suppresses IL‑1β‑induced inflammation in mouse chondrocytes by inhibiting the MAPK pathway, suggesting a promising therapeutic role for Peimine in the treatment of OA.
骨关节炎(OA)是最常见的退行性关节疾病,分泌的炎症分子在其中起着关键作用。已报道佩米诺具有抗炎活性。为了研究佩米诺在 OA 中的潜在治疗作用,将小鼠关节软骨细胞在体外用 IL-1β和不同剂量的佩米诺处理。数据显示,佩米诺不仅抑制了 IL-1β诱导的一氧化氮(NO)和前列腺素 E2 的产生,还降低了诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的蛋白水平。此外,佩米诺抑制了 IL-1β诱导的基质金属蛋白酶(MMP)-1、MMP-3、MMP-9、MMP-13、解整合素和金属蛋白酶与凝血酶敏感蛋白基序(ADAMTS)-4 和 ADAMTS-5 的 mRNA 表达。此外,佩米诺抑制了 IL-1β诱导的丝裂原活化蛋白激酶(MAPK)通路的激活。MAPK 通路的激活减弱了佩米诺对 IL-1β处理的软骨细胞的保护作用,与佩米诺组相比,MMP-3、MMP-13、ADAMTS-5、iNOS 和 COX-2 的表达水平增加。体内数据表明,佩米诺限制了小鼠模型中 OA 的发展。总的来说,数据表明佩米诺通过抑制 MAPK 通路抑制 IL-1β诱导的小鼠软骨细胞炎症,提示佩米诺在治疗 OA 方面具有有前景的治疗作用。