Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages.
Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages.
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叶酸衍生的碳点通过 NF-κB/MAPK 途径保护软骨细胞并重编程巨噬细胞，从而减轻骨关节炎
DOI：
10.1186/s12951-022-01681-6
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发表时间：
2022-11-03
影响因子：
10.2
通讯作者：
Fang, Bing
中科院分区：
文献类型：
--
作者：
Jin, Yu;Zhang, Qing;Qin, Xing;Liu, Zhen;Li, Zhenxia;Zhong, Xiaoxia;Xia, Lunguo;He, Jie;Fang, Bing
背景骨性关节炎是一种世界性的常见关节疾患，造成巨大的健康和经济负担。然而，开发一种有效的治疗方法来预防或延迟骨性关节炎仍然是一个未达到的目标。结果以叶酸为原料，水热法制备了一种具有良好生物相容性的碳点(CDs)，并能有效地减轻骨关节炎。研究表明，CDS可减轻IL-1β诱导的促炎反应、氧化应激、软骨退变和细胞外基质降解。此外，CDS对脂多糖(LPS)诱导的巨噬细胞炎症和极化具有重编程作用。CDS处理的巨噬细胞条件培养液(CM)可减轻IL1β诱导的软骨细胞损伤。此外，经CDS处理的软骨细胞的CM对巨噬细胞具有免疫调节作用。CDS从机制上抑制了IL-1κ刺激的软骨细胞中核因子-κB(NF-βB)和丝裂原活化蛋白激酶(MAPK)信号通路的激活。体内实验采用小鼠前交叉韧带切断(ACLT)模型，结果表明，CDS关节腔内注射能有效延缓OA的发生。结论CDS可通过促进软骨修复和局部微环境中巨噬细胞的免疫调节来介导OA的发生，为利用CDS作为一种新型的纳米材料治疗OA提供了依据。
BackgroundOsteoarthritis (OA) is a common joint disorder worldwide which causes great health and economic burden. However, there remains an unmet goal to develop an effective therapeutic method to prevent or delay OA. Chondrocytes, as the major cells involved in OA progression, may serve as a promising therapeutic target.ResultsA kind of carbon dots (CDs) with excellent biocompatibility was fabricated from folic acid via hydrothermal method and could effectively attenuate osteoarthritis. It was demonstrated that CDs treatment could rescue IL1β-induced proinflammatory responses, oxidative stress, cartilage degeneration and extracellular matrix degradation. Moreover, CDs reprogrammed lipopolysaccharide (LPS)-induced macrophage inflammation and polarization. Conditioned medium (CM) from CDs-treated macrophages could attenuate IL1β-induced chondrocyte injury. Also, CM from CDs-treated chondrocytes had immunoregulatory functions on macrophages. Mechanistically, CDs inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in IL1β-stimulated chondrocytes. In vivo, anterior cruciate ligament transection (ACLT) mice model was adopted and it was indicated that intra-articular injection of CDs effectively delays OA pathogenesis.ConclusionsTaken together, these findings indicated CDs could mediate OA via promoting cartilage repair and immunomodulating macrophages within local microenvironment, which may provide evidences for utilizing CDs as a novel nanomaterial for OA treatment.
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DOI：
10.1002/art.41486
发表时间：
2021-01
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Hsueh MF;Zhang X;Wellman SS;Bolognesi MP;Kraus VB
通讯作者：
Kraus VB
影响因子：
4.5
作者：
Hu X;Li R;Sun M;Kong Y;Zhu H;Wang F;Wan Q
通讯作者：
Wan Q
影响因子：
5.8
作者：
Han, Yu;Zhang, Fan;Liu, Jianguo
通讯作者：
Liu, Jianguo
影响因子：
20.3
作者：
Kondreddy, Vijay;Wang, Jue;Pendurthi, Usha R.
通讯作者：
Pendurthi, Usha R.
异常的流体剪切应力通过 H3K4me3 对 ZBTB20 的表观遗传调控促进关节软骨发病
影响因子：
4.5
作者：
Jin Y;Li Z;Wu Y;Li H;Liu Z;Liu L;Ouyang N;Zhou T;Fang B;Xia L
通讯作者：
Xia L