College of Food Science and Engineering , Ocean University of China , Qingdao , Shandong Province 266003 , China.
J Agric Food Chem. 2019 Mar 20;67(11):3125-3133. doi: 10.1021/acs.jafc.8b05841. Epub 2019 Mar 12.
Osteoarthritis (OA) is a prevalent debilitating disease which is predominantly characterized by cartilage degeneration. In the current study, destabilization of the medial meniscus (DMM) mouse model was used to investigate the effects of Antarctic krill peptides (AKP) on cartilage protection. As observed, AKP clearly ameliorate cartilage degeneration as evidenced by increased cartilage thickness and cartilage area and decreased histological Osteoarthritis Research Society International (OARSI) scores. Toluidine blue staining showed that AKO remarkably inhibited the loss of cartilage matrix in mice with OA. Hypoxia-inducible factor-2α (HIF-2α) has a key role in catabolic regulation and inflammation cascades which are the main causes of OA. AKP can down-regulate the expression of HIF-2α and its downstream genes such as MMP-13, Adamts-5, IL-1β, iNOS, CXCL-1, and NOS. Consistent with this, anabolic genes such as Acan and Col2α1 were restored after treatment with AKP. Chondrocyte apoptosis and the reduction in cartilage cell viability are also involved in the process of OA. The HIF-2α-mediated death receptor apoptosis signaling pathway has been involved in the regulation of chondrocyte apoptosis. AKP can reduce the expressions of key pro-apoptosis genes in Fas-FasL and DR3-DR3L signaling pathways such as Fas, FasL, FADD, caspase8, caspase3, DR3, DR3L, RIP, and NF-κB. In addition, expressions of antiapoptosis genes such as c-AIP and c-FLIP were increased significantly. These findings indicate that AKP can be used as a new functional factor in the development of functional foods and chondroprotective drugs.
骨关节炎（OA）是一种常见的使人虚弱的疾病，主要表现为软骨退化。在本研究中，使用内侧半月板不稳定（DMM）小鼠模型来研究南极磷虾肽（AKP）对软骨保护的影响。结果表明，AKP 明显改善了软骨退化，表现为软骨厚度和面积增加，组织学骨关节炎研究协会国际（OARSI）评分降低。甲苯胺蓝染色显示，AKO 显著抑制了 OA 小鼠软骨基质的丢失。缺氧诱导因子-2α（HIF-2α）在分解代谢调节和炎症级联反应中起关键作用，这是 OA 的主要原因。AKP 可以下调 HIF-2α及其下游基因的表达，如 MMP-13、Adamts-5、IL-1β、iNOS、CXCL-1 和 NOS。与此一致的是，AKP 处理后，合成代谢基因如 Acan 和 Col2α1 得到恢复。软骨细胞凋亡和软骨细胞活力降低也参与了 OA 的发生过程。HIF-2α 介导的死亡受体凋亡信号通路参与了软骨细胞凋亡的调节。AKP 可以降低 Fas-FasL 和 DR3-DR3L 信号通路中关键促凋亡基因的表达，如 Fas、FasL、FADD、caspase8、caspase3、DR3、DR3L、RIP 和 NF-κB。此外，抗凋亡基因如 c-AIP 和 c-FLIP 的表达明显增加。这些发现表明，AKP 可用作功能性食品和软骨保护药物开发的新功能因子。
