Unraveling the Spatial and Signaling Dynamics and Splicing Kinetics of Immune Infiltration in Osteoarthritis Synovium

Chuan Wang ¹ Zevar Zeng ² Tao Wang ¹ Zhihong Xie ¹ Jian Zhang ¹ Wentao Dong ¹ Fei Zhang ¹ Wuxun Peng ^1*

• ¹ Affiliated Hospital of Guizhou Medical University, Guiyang, China
• ² Sun Yat-sen University, Guangzhou, Guangdong Province, China

Osteoarthritis (OA) is a long-term joint disorder where the articular cartilage degeneration and synovial inflammation becomes inflamed, causing pain and reduced mobility. The synovial membrane undergoes substantial pathological changes in OA, notably marked by the infiltration of immune myeloid cells, which contribute to the chronic inflammatory environment. There is still no detailed atlas of the synovium in OA that covers both spatial and gene activity changes, despite recent technological progress. In this study, we use spatial transition tensor (STT) and intercellular flow to explore the signals that control lymphatic infiltration in the synovial membrane comparing OA and healthy knee joints. We identify distinct cell populations and their gene activity patterns, as well as with genes and transcription factors that contribute to inflammation and tissue remodeling. Importantly, we reveal the patterns of movement for both immune myeloid cells and lymphatic infiltration, highlighting the interactions between cells in OA. Additionally, we provide new insights into how myeloid and lymphoid cells communication through signaling within the synovial environment.Our findings point to possible therapeutic targets for reducing inflammation and improving synovial function. Through mapping the spatial and signaling enviroment of OA synovium, our study enhances understanding of OA development and suggest the potential of targeting immune cell signals to reduce the disease's impact.