{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:38:16Z","timestamp":1787243896122,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ22H060003"],"award-info":[{"award-number":["LQ22H060003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074472"],"award-info":[{"award-number":["82074472"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study, we investigated whether the ability of aucubin to mitigate the pathology of GONFH involves suppression of TLR4\/NF\u2010\u03baB signalling and promotion of macrophage polarization to an M2 phenotype. In necrotic bone tissues from GONFH patients, we compared levels of pro\u2010inflammatory M1 macrophages and anti\u2010inflammatory M2 macrophages as well as levels of TLR4\/NF\u2010\u03baB signalling. In a rat model of GONFH, we examined the effects of aucubin on these parameters. We further explored its mechanism of action in a cell culture model of M1 macrophages. Necrotic bone tissues from GONFH patients contained a significantly increased macrophage M1\/M2 ratio, and higher levels of TLR4, MYD88 and NF\u2010\u03baB p65 than bone tissues from patients with hip osteoarthritis. Treating GONFH rats with aucubin mitigated bone necrosis and demineralization as well as destruction of trabecular bone and marrow in a dose\u2010dependent manner, based on micro\u2010computed tomography. These therapeutic effects were associated with a decrease in the overall number of macrophages, decrease in the proportion of M1 macrophages, increase in the proportion of M2 macrophages, and downregulation of TLR4, MYD88 and NF\u2010\u03baB p65. These effects in\u00a0vivo were confirmed by treating cultures of M1 macrophage\u2010like cells with aucubin. Aucubin mitigates bone pathology in GONFH by suppressing TLR4\/NF\u2010\u03baB signalling to shift macrophages from a pro\u2010 to anti\u2010inflammatory phenotype.<\/jats:p>","DOI":"10.1111\/jcmm.18583","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T23:59:51Z","timestamp":1723247991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Aucubin suppresses\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    signalling to shift macrophages toward\n                    <scp>M2<\/scp>\n                    phenotype in glucocorticoid\u2010associated osteonecrosis of the femoral head"],"prefix":"10.1111","volume":"28","author":[{"given":"Chen","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Orthopedics Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofeng","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Luoyang Central Hospital Affiliated to Zhengzhou University  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province  Luoyang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province  Luoyang Henan 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