Department of Orthopedics and Traumatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.
Mod Rheumatol. 2020 Jul;30(4):758-764. doi: 10.1080/14397595.2019.1651445. Epub 2019 Aug 19.
Cytokines in synovial fluid (SF) play a crucial role in knee osteoarthritis (KOA). Exosomes are nanovesicles that are abundant in SF and carry a large quantity of signaling molecules. The purpose of this study was to evaluate the cytokine profiles of SF-derived exosomes and try to explore its biological function. Twenty-four KOA patients who were scheduled for their first intra-articular injection or knee replacement surgery were enrolled and divided into the KL1-2 group and the KL3-4 group according to the Kellgren and Lawrence (KL) classification. SF was collected from the patient's knee for the isolation of exosomes. A multiplex cytokine assay was performed to detect the 21 cytokines in the exosomes. The SF derived-exosomes were exposed to PBMCs and chondrocytes to assess their immunomodulatory potential. Exosomes were successfully extracted from the SF, with an average diameter of 92 nm. Most cytokines were detectable in the SF-derived exosomes. Twelve inflammatory cytokines and eight chemokines were elevated in the exosomes of the KL3-4 group compared to that of the KL1-2 group ( < .05). A higher number of PBMCs were chemo attracted and the proliferation of chondrocytes was restrained by the SF-derived exosomes from the KL3-4 group in comparison with the KL1-2 group ( < .05). Our data indicated that most cytokines in SF are not only in a free form but also associated with and enriched in exosomes. Exosomes from end-stage KOA patients have a higher level of cytokines, especially chemokines, in comparison with the cytokine profiles of the soluble SF. SF-derived exosomes recruit inflammatory cells and inhibit cartilage proliferation, thus promoting joint degeneration. These data provide a new perspective for understanding the changes in the inner environment of KOA.
滑液中的细胞因子在膝骨关节炎 (KOA) 中起着至关重要的作用。外泌体是富含于滑液中的纳米囊泡，携带大量信号分子。本研究旨在评估滑液来源的外泌体中的细胞因子谱，并尝试探索其生物学功能。
将 24 例拟行关节腔内注射或膝关节置换术的 KOA 患者纳入研究，并根据 Kellgren 和 Lawrence (KL) 分级分为 KL1-2 组和 KL3-4 组。从患者膝关节采集滑液用于外泌体分离。采用多重细胞因子检测法检测外泌体中的 21 种细胞因子。将 SF 衍生的外泌体暴露于 PBMC 和软骨细胞中，以评估其免疫调节潜能。
成功从 SF 中提取外泌体，平均直径为 92nm。大多数细胞因子在外泌体中均可检测到。与 KL1-2 组相比，KL3-4 组外泌体中 12 种炎症细胞因子和 8 种趋化因子升高（<0.05）。与 KL1-2 组相比，KL3-4 组 SF 衍生的外泌体可吸引更多的 PBMC 趋化，并抑制软骨细胞增殖（<0.05）。
我们的数据表明，SF 中的大多数细胞因子不仅以游离形式存在，而且还与外泌体结合并在外泌体中富集。与可溶性 SF 的细胞因子谱相比，终末期 KOA 患者的外泌体中细胞因子，尤其是趋化因子水平更高。SF 衍生的外泌体募集炎症细胞并抑制软骨增殖，从而促进关节退变。这些数据为理解 KOA 内在环境变化提供了新的视角。
