Casticin suppresses monoiodoacetic acid-induced knee osteoarthritis through inhibiting HIF-1α/NLRP3 inflammasome signaling
Casticin suppresses monoiodoacetic acid-induced knee osteoarthritis through inhibiting HIF-1α/NLRP3 inflammasome signaling
复制标题
Casticin 通过抑制 HIF-1 α/NLRP3 炎症小体信号传导抑制单碘乙酸诱导的膝骨关节炎
DOI：
10.1016/j.intimp.2020.106745
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发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Wang, Peimin
中科院分区：
文献类型：
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作者：
Li, Xiaochen;Mei, Wei;Wang, Peimin
膝关节骨关节炎（KOA）是一种致残性慢性炎症性疾病，与滑膜组织缺氧和滑膜纤维化密切相关。紫花牡荆素是从中药蔓荆子中提取的一种化合物，在以往的研究中已被证明具有预防炎症和纤维化的作用。然而，紫花苜蓿素对KOA滑膜纤维化的影响尚不清楚。在本研究中，我们的目的是探讨如何紫花苜蓿素影响滑膜纤维化的单碘乙酸（MIA）诱导的KOA大鼠。建立MIA诱导的膝关节骨性关节炎模型和脂多糖（LPS）刺激的原代滑膜成纤维细胞炎症模型。采用H&E和天狼星红染色法观察滑膜组织的病理学和形态学变化。采用哌莫硝唑染色和缺氧诱导因子1 α（HIF-1 α）免疫组化检测滑膜组织缺氧情况。通过蛋白质印迹、qRT-PCR或ELISA检测KOA大鼠模型和原代滑膜成纤维细胞中核苷酸寡聚化结构域样受体蛋白3（NLRP 3）炎性体组分、纤维化标志物（TGF-β、COL 1A 1和TIMP 1）和炎性细胞因子的水平。提示紫花牡荆素可改善大鼠滑膜组织缺氧、炎症及滑膜纤维化。此外，紫花苜蓿素抑制MIA诱导的KOA大鼠和滑膜成纤维细胞中NLRP 3炎性体的活化。总之，我们的研究结果表明，紫花牡荆素减轻MIA诱导的KOA抑制HIF-1 α/NLRP 3炎性体激活。因此，紫花苜蓿素可能是一种潜在的治疗KOA的策略。
Knee osteoarthritis (KOA) is a disabling chronic inflammatory disease that is closely associated with synovium tissue hypoxia and synovial fibrosis. Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proved effective in preventing inflammation and fibrosis in previous studies. However, the effect of casticin on synovial fibrosis in KOA is not clear. In present study, we aimed to investigate how did casticin affect synovial fibrosis on monoiodoacetic acid (MIA)-induced KOA in rats. The MIA-induced knee osteoarthritis model and lipopolysaccharide (LPS) stimulated primary synovial fibroblasts inflammation model were established. Pathological and morphological changes in synovial tissue were observed by H&E and sirius red staining. The hypoxia of synovium was detected by pimonidazole staining and immunohistochemistry of hypoxia-inducible factors 1 alpha (HIF-1 alpha). The levels of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome components, fibrogenic markers (TGF-beta, COL1A1 and TIMP1) and inflammatory cytokines were examined by western blotting, qRT-PCR or ELISA in both KOA rat models and primary synovial fibroblasts. Our data suggested that casticin improved hypoxia and inflammation in synovium tissue, as well the synovial fibrosis in rats. Besides, casticin inhibited the activation of NLRP3 inflammasome in MIA-induced KOA rats and synovial fibroblasts. In conclusion, our findings demonstrated that casticin alleviated MIA-induced KOA by inhibiting of HIF-1 alpha/NLRP3 inflammasome activation. Therefore, casticin could be a potential treatment strategy for KOA.