Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, 500 Quxi Road, Shanghai, 200011, China.
State Key Laboratory of Advanced Optical Communication Systems and Networks, Key Laboratory for Laser Plasmas (Ministry of Education), School of Physics and Astronomy, Shanghai Jiao Tong University, No. 800, Dongchuan Road, Minhang District, Shanghai, 200240, China.
J Nanobiotechnology. 2022 Nov 3;20(1):469. doi: 10.1186/s12951-022-01681-6.
Osteoarthritis (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.
A 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.
Taken 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.
骨关节炎（OA）是一种全球范围内常见的关节疾病，给健康和经济带来了巨大的负担。然而，目前仍未找到一种有效的治疗方法来预防或延缓 OA 的发生。软骨细胞作为 OA 进展过程中的主要细胞，可能成为一种有前途的治疗靶点。
通过水热法从叶酸中制备出一种具有优异生物相容性的碳点（CDs），可有效减轻骨关节炎。研究表明，CDs 治疗可挽救 IL1β 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 可重新编程脂多糖（LPS）诱导的巨噬细胞炎症和极化。来自 CDs 处理的巨噬细胞的条件培养基（CM）可减轻 IL1β 诱导的软骨细胞损伤。此外，来自 CDs 处理的软骨细胞的 CM 对巨噬细胞具有免疫调节功能。机制上，CDs 抑制了 IL1β 刺激的软骨细胞中核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路的激活。在体内，采用前交叉韧带切断（ACLT）小鼠模型，结果表明关节内注射 CDs 可有效延缓 OA 的发病机制。
综上所述，这些发现表明 CDs 可通过促进软骨修复和调节局部微环境中的巨噬细胞来介导 OA，这可为利用 CDs 作为 OA 治疗的新型纳米材料提供依据。
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