{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:42:26Z","timestamp":1787013746441,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Steroid\u2010induced osteonecrosis of the femoral head (SONFH) is characterized by impaired osteogenesis in bone marrow mesenchymal stem cells (BMSCs). This study investigates the role of lysine\u2010specific demethylase 5A (KDM5A) in SONFH to identify potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human BMSCs were isolated and characterized for cell surface markers and differentiation capacity. A SONFH cell model was established using dexamethasone treatment. BMSCs were transfected with KDM5A overexpression vectors or si\u2010KDM5A, and the expression of KDM5A, miR\u2010107, runt\u2010related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) was assessed. Alizarin red staining was used to observe mineralization nodules, while alkaline phosphatase activity and cell viability were measured. The enrichment of KDM5A and histone 3 lysine 4 trimethylation (H3K4me3) on the promoters of RUNX2, OCN, and OPN was analyzed. The binding between miR\u2010107 and KDM5A 3\u2032UTR was validated, and the combined effect of miR\u2010107 overexpression and KDM5A overexpression on BMSC osteogenic differentiation was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>KDM5A was upregulated in BMSCs from SONFH. Inhibition of KDM5A promoted osteogenic differentiation of BMSCs, associated with increased RUNX2, OCN, and OPN promoters. KDM5A bound to the promoters of RUNX2, OCN, and OPN, leading to reduced H3K4me3 levels and downregulation of their expression. Overexpression of miR\u2010107 inhibited KDM5A and enhanced BMSC osteogenic differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>KDM5A negatively regulates BMSC osteogenic differentiation by modulating H3K4me3 levels on the promoters of key osteogenic genes. miR\u2010107 overexpression counteracts the inhibitory effect of KDM5A on osteogenic differentiation. These findings highlight the potential of targeting the KDM5A\/miR\u2010107 axis for SONFH therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.15090","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T23:24:12Z","timestamp":1709681052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mechanism of\n                    <scp>KDM5A<\/scp>\n                    \u2010mediated\n                    <scp>H3K4me3<\/scp>\n                    modification in the osteogenic differentiation of mesenchymal stem cells in steroid\u2010induced osteonecrosis of the femoral head"],"prefix":"10.1111","volume":"27","author":[{"given":"Yi","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Orthopedics Xiangtan Central Hospital  Xiangtan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Adult Emergency Boai Hospital  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Xiangtan Central Hospital  Xiangtan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1923-6187","authenticated-orcid":false,"given":"Liang","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Xiangtan Central Hospital  Xiangtan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.777697"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-018-3994-8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1498-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03027-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29161"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.14451"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2020.06.022"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2992"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S255276"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112314"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2023.2268813"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6472864"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.238"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2020.1743536"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2022.02.006"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8140595"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13898"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13202"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103341"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.11.213"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05005"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206239"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1141"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.05.004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.11.079"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X10666150528153313"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00472-6"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arth.2015.08.017"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2021.10.009"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02852-w"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.581545"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121693"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.05.011"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-023-04903-8"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/kjm2.12426"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2019.02.003"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2021.12.002"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.15090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T05:42:13Z","timestamp":1711431733000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.15090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/1756-185X.15090"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.15090","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-11-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15090"}}