Liao Bo, Tian Yu, Guan Mengtong, Han Wang, Yi Weiwei, Li Kaiting, Yang Xiaoliang, Niu Yajuan, Zhang Bin, Teng Peiyu, Bai Dingqun, Kuang Liang, Zhu Ying, Han Xiaoyu
Department of Rehabilitation Medicine, Key Laboratory of Physical Medicine and Precision Rehabilitation of Chongqing Municipal Health Commission, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
Center of Bone Metabolism and Repair Laboratory for Prevention and Rehabilitation of Training Injuries State Key Laboratory of Trauma Burns and Combined Injury Trauma Center Research Institute of Surgery Daping, Hospital Army Medical University, Third Military Medical University, Chongqing, 400000, P.R. China.
J Nanobiotechnology. 2025 Jul 16;23(1):522. doi: 10.1186/s12951-025-03591-9.
Synovial inflammation is a pivotal factor in the pathogenesis of osteoarthritis (OA). Platelet-rich plasma-derived Exosomes (PRP-Exos), known for their low immunogenicity, have demonstrated efficacy in modulating chondrocyte function. However, the specific effects and mechanisms of PRP-Exos in synovial inflammation remain unclear. This study aimed to investigate the therapeutic effects and mechanisms of PRP-Exos in synovial inflammation induced by destabilization of the medial meniscus (DMM) in mice.
PRP-Exos were extracted via ultracentrifugation. In vivo experiments revealed that PRP-Exos alleviated pain behaviors and synovial inflammation in DMM mice. Furthermore, it was discovered that PRP-Exos enhanced the synovial lymphatic function in DMM mice and promoted lymphangiogenesis. Meanwhile, the therapeutic effect of PRP-Exos on synovial inflammation was attenuated after inhibition of lymphatic function. In vitro studies demonstrated that PRP-Exos enhanced the proliferation, migration, and tube formation ability of lymphatic endothelial cells (LECs), via regulating the PI3K/Akt signaling pathway.
This research is the first to reveal that PRP-Exos alleviate pain behaviors and synovial inflammation in DMM mice through activation of the PI3K/Akt signaling pathway in LECs, thereby enhancing synovial lymphatic function and promoting the clearance of inflammatory cells and associated cytokines. These findings offer a novel theoretical foundation for the treatment of synovial inflammation and other inflammation-associated disorders.
滑膜炎症是骨关节炎（OA）发病机制中的关键因素。富含血小板血浆来源的外泌体（PRP-Exos）以其低免疫原性而闻名，已证明在调节软骨细胞功能方面具有功效。然而，PRP-Exos在滑膜炎症中的具体作用和机制仍不清楚。本研究旨在探讨PRP-Exos对小鼠内侧半月板不稳定（DMM）诱导的滑膜炎症的治疗作用及机制。
通过超速离心提取PRP-Exos。体内实验表明，PRP-Exos减轻了DMM小鼠的疼痛行为和滑膜炎症。此外，发现PRP-Exos增强了DMM小鼠的滑膜淋巴功能并促进了淋巴管生成。同时，抑制淋巴功能后，PRP-Exos对滑膜炎症的治疗作用减弱。体外研究表明，PRP-Exos通过调节PI3K/Akt信号通路增强了淋巴管内皮细胞（LECs）的增殖、迁移和管形成能力。
本研究首次揭示PRP-Exos通过激活LECs中的PI3K/Akt信号通路减轻DMM小鼠的疼痛行为和滑膜炎症，从而增强滑膜淋巴功能并促进炎性细胞和相关细胞因子的清除。这些发现为滑膜炎症和其他炎症相关疾病的治疗提供了新的理论基础。
