Zhang, WeiweiLi, XinleLi, JieWang, XiaoyuLiu, DaquanZhai, LidongDing, BeibeiLi, GuangSun, YutingYokota, HirokiZhang, Ping2024-05-022024-05-022021-06-14Zhang W, Li X, Li J, et al. Mechanical Loading Mitigates Osteoarthritis Symptoms by Regulating the Inflammatory Microenvironment. Published online June 14, 2021. doi:10.2139/ssrn.3866409https://hdl.handle.net/1805/40421Osteoarthritis (OA) is one of the most common chronic diseases, in which inflammatory responses in the articular cavity induce chondrocyte apoptosis and cartilage degeneration. While mechanical loading is reported to mitigate synovial inflammation, the mechanism and pathways for the loading-driven improvement of OA symptoms remain unclear. In this research, we evaluated the loading effects on the M1/M2 polarization of synovial macrophages via performing molecular, cytology, and histology analyses. In the OA groups, the cell layer of the synovial lining was enlarged with an increase in cell density. Also, M1 macrophages were polarized and pro-inflammatory cytokines were increased. In contrast, in the OA group with mechanical loading cartilage degradation was reduced and synovial inflammation was alleviated. Notably, the polarization of M1 macrophages was diminished by mechanical loading, while that of M2 macrophages was increased. Furthermore, mechanical loading decreased the levels of pro-inflammatory cytokines such as IL-1β and TNF-α and suppressed PI3K/AKT/NF-κB signaling. Consistently, NF-κB inhibited decreased the polarization of M1 macrophages in RAW264.7 macrophages. Taken together, this study demonstrates that mechanical loading changes the ratio of M1 and M2 macrophage polarization via regulating PI3K/AKT/NF-κB signaling and provides chondroprotective effects in the mouse OA model.en-USPublisher PolicyInflammatory microenvironmentMacrophage polarizationMechanical loadingOsteoarthritisPI3K/AKT/NF-κB signalingArticle