Crosstalk between lymphatic system and synovial inflammatory cells in osteoarthritis: molecular mechanisms and potential cell-based therapies.

The lymphatic system plays a significant part in interstitial fluid balance and immune surveillance throughout the whole body. In addition, recent studies have elucidated the role of the lymphatic system in maintaining the normal function of joints, and its dysfunction is related to the pathogenesis of osteoarthritis (OA). In this review, we described the composition and function of the lymphatic system in the knee joints and summarized the research progress of lymphatic networks in the development of OA. The synovial lymphatic system (SLS) is the most well-characterized lymphatic network, and we elaborated the pathological changes of SLS which resulted in the disturbance of knee joint homeostasis and the progression of OA. We summarized the underlying molecular mechanisms of lymphatic disorders and focused on the crosstalk between the SLS and synovial inflammatory cells, especially the abnormal macrophage polarization and regulatory T cells dysfunction. Cell-based therapies have been proven to restore lymphatic function. This review proposed potential cell-based therapies to treat OA by targeting the SLS, and mesenchymal stem cells and Tregs based therapies are currently the most promising approaches to treat OA by restoring lymphatic flow.