Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
J Transl Med. 2022 Sep 23;20(1):428. doi: 10.1186/s12967-022-03515-3.
Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation. The targeting of CCL2-CCR2 is being studied as part of various topics including the treatment of OA.
In this study, we evaluated the potential therapeutic effects the sCCR2 E3 gene may exert on OA. The effects of sCCR2 E3 were investigated in animal experiments consisting of intra-articular injection of sCCR2 E3 in a monosodium iodoacetate (MIA)-induced OA rat model. The effects after intra-articular injection of sCCR2 E3 (fusion protein encoding 20 amino acids of the E3 domain of the CCL2 receptor) in a monosodium iodoacetate-induced OA rat model were compared to those in rats treated with empty vector (mock treatment) and full-length sCCR2.
Pain improved with expression of the sCCR2 gene. Improved bone resorption upon sCCR2 E3 gene activation was confirmed via bone analyses using micro-computed tomography. Histologic analyses showed that the sCCR2 E3 gene exerted protective effects against cartilage damage and anti-inflammatory effects on joints and the intestine.
These results show that sCCR2 E3 therapy is effective in reducing pain severity, inhibiting cartilage destruction, and suppressing intestinal damage and inflammation. Thus, sCCR2 E3 may be a potential therapy for OA.
骨关节炎（OA）是最常见的退行性关节炎类型，影响整个关节，导致疼痛、关节炎症和软骨损伤。各种风险因素与 OA 的发生有关，近年来，人们对 OA 中的慢性低度炎症产生了浓厚的研究兴趣。单核细胞趋化蛋白-1（MCP-1；也称为 CCL2）通过单核细胞中的 C-C 趋化因子受体 2（CCR2）起作用，是单核细胞的趋化因子，在炎症的启动中起着重要作用。CCL2-CCR2 的靶向作用正在作为包括 OA 治疗在内的各种主题的一部分进行研究。
在这项研究中，我们评估了 sCCR2 E3 基因对 OA 可能产生的潜在治疗效果。在包括关节内注射 sCCR2 E3 的动物实验中研究了 sCCR2 E3 的作用，在该实验中，在碘酸钠（MIA）诱导的 OA 大鼠模型中进行了 sCCR2 E3 的关节内注射。在碘酸钠诱导的 OA 大鼠模型中关节内注射 sCCR2 E3（CCL2 受体 E3 结构域 20 个氨基酸的融合蛋白）与空载体（模拟治疗）和全长 sCCR2 治疗的效果进行了比较。
sCCR2 基因的表达改善了疼痛。通过使用微计算机断层扫描对骨骼进行分析，证实了 sCCR2 E3 基因激活后对骨吸收的改善。组织学分析表明，sCCR2 E3 基因对软骨损伤具有保护作用，并对关节和肠道具有抗炎作用。
这些结果表明，sCCR2 E3 治疗可有效减轻疼痛严重程度，抑制软骨破坏，并抑制肠道损伤和炎症。因此，sCCR2 E3 可能是 OA 的一种潜在治疗方法。
