D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner.
D-mannose alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis in a HIF-2α-dependent manner.
复制标题
DOI：
10.1111/cpr.13134
复制
发表时间：
2021-11
影响因子：
8.5
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Zhou X;Zheng Y;Sun W;Zhang Z;Liu J;Yang W;Yuan W;Yi Y;Wang J;Liu J
软骨细胞铁凋亡有助于骨关节炎（OA）的进展，D-甘露糖在许多炎症性疾病中显示出治疗价值。在这里，我们研究了在骨关节炎软骨变性过程中D-甘露糖是否干扰软骨细胞铁凋亡细胞死亡。采用体内前交叉韧带横断（ACLT）诱导的OA小鼠模型和白细胞介素-1 β（IL-1β）暴露诱导的OA微环境中软骨细胞的体外研究。结合Epas 1基因功能获得和丧失、组织学、免疫荧光、定量RT-PCR、Western blot、细胞活力和流式细胞术实验，评价D-甘露糖在OA进展中的软骨保护作用以及缺氧诱导因子2 α（HIF-2 α）在D-甘露糖诱导的软骨细胞抗铁凋亡中的作用。D-甘露糖通过减弱软骨细胞对铁凋亡的敏感性和缓解OA进展来发挥软骨保护作用。HIF-2α被鉴定为D-甘露糖诱导的软骨细胞抗铁凋亡的中心介质。此外，通过关节内注射Ad‐ Epas 1在软骨细胞中过表达HIF‐2α，消除了D‐甘露糖在OA进展过程中的软骨保护作用，并消除了D‐甘露糖作为铁凋亡抑制剂的作用。D-甘露糖通过抑制HIF-2α介导的软骨细胞对铁凋亡的敏感性来延缓骨关节炎的进展，表明D-甘露糖是铁凋亡相关疾病的潜在治疗策略。D‐甘露糖通过抑制软骨退化有效地延缓骨关节炎进展。D-甘露糖通过减弱对铁下垂的敏感性来保护骨关节炎软骨细胞。HIF-2α在增强软骨细胞对铁凋亡的易感性中至关重要。HIF-2α是D-甘露糖诱导的铁凋亡抵抗的中心介质。
Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D‐mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether D‐mannose interferes in chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. In vivo anterior cruciate ligament transection (ACLT)‐induced OA mouse model and an in vitro study of chondrocytes in an OA microenvironment induced by interleukin‐1β (IL‐1β) exposure were employed. Combined with Epas1 gene gain‐ and loss‐of‐function, histology, immunofluorescence, quantitative RT‐PCR, Western blot, cell viability and flow cytometry experiments were performed to evaluate the chondroprotective effects of D‐mannose in OA progression and the role of hypoxia‐inducible factor 2 alpha (HIF‐2 α) in D‐mannose‐induced ferroptosis resistance of chondrocytes. D‐mannose exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviated OA progression. HIF‐2α was identified as a central mediator in D‐mannose‐induced ferroptosis resistance of chondrocytes. Furthermore, overexpression of HIF‐2α in chondrocytes by Ad‐Epas1 intra‐articular injection abolished the chondroprotective effect of D‐mannose during OA progression and eliminated the role of D‐mannose as a ferroptosis suppressor. D‐mannose alleviates osteoarthritis progression by suppressing HIF‐2α‐mediated chondrocyte sensitivity to ferroptosis, indicating D‐mannose to be a potential therapeutic strategy for ferroptosis‐related diseases. D‐Mannose effectively alleviates osteoarthritis progression by suppressing cartilage degeneration. D‐mannose protects osteoarthritic chondrocytes by attenuating sensitivity to ferroptosis. HIF‐2α is vital in potentiating the susceptibility of chondrocytes to ferroptosis. HIF‐2α is a central mediator in D‐mannose‐induced ferroptosis resistance.
登录
查看更多内容
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
9
作者：
Liu Y;Xu S;Zhang H;Qian K;Huang J;Gu X;Li Y;Fan Y;Hu J
通讯作者：
Hu J
影响因子：
7.5
作者：
Lin, Zhiming;Miao, Jianing;Bai, Lunhao
通讯作者：
Bai, Lunhao
影响因子：
--
作者：
Bohensky, Jolene;Terkhorn, Shawn P.;Freeman, Theresa A.;Adams, Christopher S.;Garcia, Joseph A.;Shapiro, Irving M.;Srinivas, Vickram
通讯作者：
Srinivas, Vickram
D-甘露糖通过抑制 IL-6 分泌增强牙周膜干细胞的免疫调节
影响因子：
4.3
作者：
Guo, Lijia;Hou, Yanan;Bai, Yuxing
通讯作者：
Bai, Yuxing