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While mechanical loading is reported to mitigate synovial inflammation, the mechanism and pathways for the loading\u2010driven improvement of OA symptoms remain unclear. In this study, we evaluated the loading effects on M1\/M2 polarization of synovial macrophages via performing histology, cytology, and molecular analyses. In the OA group, the cell layer of the synovial lining was enlarged with an increase in cell density. Also, M1 macrophages were polarized and proinflammatory cytokines were increased. In contrast, in the OA group with mechanical loading, cartilage degradation was reduced and synovial inflammation was alleviated. Notably, the M1 macrophages were diminished by mechanical loading, while M2 macrophages were increased. Furthermore, mechanical loading decreased the levels of proinflammatory cytokines, such as interleukin\u20101 beta and tumor necrosis factor\u2010\u03b1, and suppressed PI3K\/AKT\/NF\u2010\u03baB signaling. Taken together, this study demonstrates that mechanical loading changes the ratio of M1 and M2 macrophages via regulation of PI3K\/AKT\/NF\u2010\u03baB signaling and provides cartilage protection in the mouse OA model.<\/jats:p>","DOI":"10.1111\/nyas.14760","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T23:34:34Z","timestamp":1646004874000},"page":"141-153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Mechanical loading mitigates osteoarthritis symptoms by regulating the inflammatory microenvironment in a mouse model"],"prefix":"10.1111","volume":"1512","author":[{"given":"Weiwei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University  Tianjin 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