{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:02:57Z","timestamp":1790013777217,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010903","name":"Key Programme","doi-asserted-by":"publisher","award":["81830079"],"award-info":[{"award-number":["81830079"]}],"id":[{"id":"10.13039\/501100010903","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2507600"],"award-info":[{"award-number":["2023YFC2507600"]}],"id":[{"id":"10.13039\/501100012166","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":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) has been identified as a hindrance to osteoblast differentiation, thereby contributing significantly to the development of osteomyelitis. Consequently, exploring pharmaceutical interventions targeting osteoblast differentiation mediated by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    may present a novel approach for treating osteomyelitis. It has been reported that N6\u2010methyladenosine (m6A) methylation is highly associated with infection. Moreover, studies continue to validate that short\u2010chain fatty acids play an important role in transcriptional modification and have been considered as a potential treatment for\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    infection. Our research aimed to examine the impact and underlying mechanism of butyrate, a short\u2010chain fatty acid, in reducing the inhibitory influence exerted by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    on osteoblast differentiation. The concentration of butyrate beneficial to MC3T3\u2010E1 cell viability was screened by Cell Counting Kit\u20108 (CCK8) assay. Reverse transcription\u2010quantitative PCR (RT\u2010qPCR), Western blotting, and alkaline phosphatase (ALP)staining were used to verify the osteogenic indexes and the expression levels of m6A methylation\u2010related proteins in MC3T3\u2010E1 cells infected with\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    at different time points. Besides, the same methods were used to verify the effects of butyrate stimulation and METTL3 knockdown on the osteogenic ability of MC3T3\u2010E1 cells. H&amp;E staining, Goldner staining, and immunohistochemical staining were used to verify the effect of butyrate on mice with endo\u2010plant associated\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    osteomyelitis. The potential mechanisms of METTL3 and autophagy in MC3T3\u2010E1 cells were studied by Western blotting. In\u00a0vitro experiments, we found that butyrate significantly enhanced the expression of osteogenic\u2010related genes down\u2010regulated by infection in MC3T3\u2010E1 cells induced by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    , including RUNX2, OCN, and ALP. In addition, METTL3, an important m6A methyltransferase, was significantly up\u2010regulated in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    \u2010infected MC3T3\u2010E1 cells, but its expression could be down\u2010regulated by butyrate. Inhibiting the expression of METTL3 by siRNA could effectively rescue the osteogenic markers down\u2010regulated by\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infection in MC3T3\u2010E1 cells, which was similar to the results of butyrate treatment. In\u00a0vivo experiments had shown that butyrate could alleviate inflammation and osteogenic activity in implant\u2010associated osteomyelitis. The construction of bone marrow METTL3 low\u2010expression mice using siRNA also showed similar effects on osteogenic activity. Additionally, Western blotting confirmed that knocking down METTL3 rescued the autophagy imbalance caused by\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infection in MC3T3\u2010E1 cells. In general, our research demonstrated that butyrate effectively alleviated the hindrance of osteoblast activity induced by\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    infection by suppressing the expression of METTL3, suggesting that butyrate may be a novel treatment for\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    osteomyelitis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70683","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T16:57:11Z","timestamp":1756745831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Butyrate Reducing Bone Mass Loss by Regulating the Expression of\n                    <scp>m6A<\/scp>\n                    Methyltransferase\n                    <scp>METTL3<\/scp>\n                    in Implant\u2010Associated\n                    <scp>\n                      <i>Staphylococcus aureus<\/i>\n                    <\/scp>\n                    Osteomyelitis"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7962-5256","authenticated-orcid":false,"given":"Chongkai","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyou","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00084-17"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1302\/2058-5241.1.000017"},{"key":"e_1_2_8_4_1","first-page":"837","article-title":"Trends in the Epidemiology of Osteomyelitis: A Population\u2010Based Study, 1969 to 2009","volume":"97","author":"Kremers H. M.","year":"2015","journal-title":"Journal of Bone and Joint Surgery. American Volume"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00134-14"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S346627"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(75)90158-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-018-0069-8"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0174-4"},{"key":"e_1_2_8_10_1","first-page":"1631","article-title":"METTL3 Plays Multiple Functions in Biological Processes","volume":"10","author":"Liu S.","year":"2020","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01231-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.687"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-020-01450-1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.04.025"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0168-5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-221091"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20200282"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxaa097"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665110004039"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1079\/PNS2002213"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/133.11.3717"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.10.013"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2622"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-023-01487-9"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15042"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019101029"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13145"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00682-3"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.930511"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2020.104431"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197001222820406"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-10-158"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2021.03.030"},{"key":"e_1_2_8_34_1","first-page":"308","article-title":"Advances in Bone Biology: The Osteoclast","volume":"17","author":"Roodman G. D.","year":"1996","journal-title":"Endocrine Reviews"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20071694"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm1511"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19124071"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.02.018"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27248715"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70683","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.70683","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T10:27:34Z","timestamp":1779704854000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":38,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/jcmm.70683"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70683","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2024-03-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70683"}}