Blockade of IL-33 signalling attenuates osteoarthritis.
Blockade of IL-33 signalling attenuates osteoarthritis.
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DOI：
10.1002/cti2.1187
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发表时间：
2020
影响因子：
5.8
通讯作者：
Sacitharan PK
中科院分区：
文献类型：
--
作者：
He Z;Song Y;Yi Y;Qiu F;Wang J;Li J;Jin Q;Sacitharan PK
骨关节炎 (OA) 是最常见的关节炎形式，其特征是软骨退化、滑膜炎和疼痛。目前还没有针对 OA 的疾病缓解疗法。未满足的关键需求是找到减少疾病进展和疼痛的治疗靶点。细胞因子 IL-33 及其受体 ST2 已被证明在免疫和炎症疾病中发挥作用，但它们在骨关节炎中的作用尚不清楚。检查非 OA 和 OA 人软骨细胞样本的 IL-33 和 ST2 表达。生成新型诱导型软骨特异性敲除小鼠 (IL-33Acan CreERT2) 和诱导型成纤维细胞样滑膜细胞敲除小鼠 (IL-33Col1a2 CreERT2) 并进行实验性 OA 模型。此外，在实验性 OA 研究中，野生型小鼠关节内注射了 IL-33 或 ST2 中和抗体。 IL-33 及其受体 ST2 在 OA 患者和小鼠疾病模型中表达增加。施用重组 IL-33 会增加体内 OA 和疼痛。滑膜成纤维细胞特异性删除 IL-33 可减少滑膜炎，但不会影响疾病结果，而软骨特异性删除 IL-33 可改善体内疾病结果。阻断 IL-33 信号传导还可以减少人和小鼠软骨细胞中软骨降解酶的释放。最重要的是，我们证明使用抗 IL-33 和 ST2 的单克隆抗体可以减轻体内 OA 和疼痛。总体而言，我们的数据表明阻断 IL-33 信号传导是 OA 的可行治疗靶点。在这项研究中，我们发现人类和小鼠骨关节炎 (OA) 样本中 IL-33 和 ST2 的表达增加。我们还证明 OA 期间 IL-33 的主要来源是软骨细胞而不是滑膜成纤维细胞。最重要的是，中和 IL-33 和 ST2 可减轻 OA 和疼痛。
Osteoarthritis (OA) is the most common form of arthritis characterised by cartilage degradation, synovitis and pain. Disease modifying treatments for OA are not available. The critical unmet need is to find therapeutic targets to reduce both disease progression and pain. The cytokine IL‐33 and its receptor ST2 have been shown to play a role in immune and inflammatory diseases, but their role in osteoarthritis is unknown. Non‐OA and OA human chondrocytes samples were examined for IL‐33 and ST2 expression. Novel inducible cartilage specific knockout mice (IL‐33Acan CreERT2) and inducible fibroblast‐like synoviocyte knockout mice (IL‐33Col1a2 CreERT2) were generated and subjected to an experimental OA model. In addition, wild‐type mice were intra‐articularly administered with either IL‐33‐ or ST2‐neutralising antibodies during experimental OA studies. IL‐33 and its receptor ST2 have increased expression in OA patients and a murine disease model. Administering recombinant IL‐33 increased OA and pain in vivo. Synovial fibroblast‐specific deletion of IL‐33 decreased synovitis but did not impact disease outcomes, whilst cartilage‐specific deletion of IL‐33 improved disease outcomes in vivo. Blocking IL‐33 signalling also reduced the release of cartilage‐degrading enzymes in human and mouse chondrocytes. Most importantly, we show the use of monoclonal antibodies against IL‐33 and ST2 attenuates both OA and pain in vivo. Overall, our data reveal blockade of IL‐33 signalling as a viable therapeutic target for OA. In this study, we found that expression of IL‐33 and ST2 is increased in human and murine osteoarthritis (OA) samples. We also demonstrate that the main sources of IL‐33 during OA are chondrocytes and not synovial fibroblasts. Most importantly, neutralising IL‐33 and ST2 attenuates OA and pain.
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影响因子：
4.5
作者：
Hong YS;Moon SJ;Joo YB;Jeon CH;Cho ML;Ju JH;Oh HJ;Heo YJ;Park SH;Kim HY;Min JK
通讯作者：
Min JK
受损关节软骨细胞释放的双链 RNA 通过 Toll 样受体 3-interleukin-33 途径促进软骨退化
影响因子：
9
作者：
Li C;Chen K;Kang H;Yan Y;Liu K;Guo C;Qi J;Yang K;Wang F;Guo L;He C;Deng L
通讯作者：
Deng L
DOI：
10.1073/pnas.1308651110
发表时间：
2013-09-10
影响因子：
11.1
作者：
Liu, Xi;Hammel, Michal;Wang, Xinquan
通讯作者：
Wang, Xinquan
影响因子：
5.1
作者：
Peng, Ge;Mu, Zhenzhen;Han, Xiuping
通讯作者：
Han, Xiuping
影响因子：
12.4
作者：
Kim, Y. H.;Yang, T. Y.;Jang, T. Y.
通讯作者：
Jang, T. Y.