{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T15:03:22Z","timestamp":1769180602246,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Yoshida Foundation for Academic and Educational Promotion","award":["21H03145"],"award-info":[{"award-number":["21H03145"]}]},{"name":"The Yoshida Foundation for Academic and Educational Promotion","award":["23K21495"],"award-info":[{"award-number":["23K21495"]}]},{"name":"The Yoshida Foundation for Academic and Educational Promotion","award":["25K13154"],"award-info":[{"award-number":["25K13154"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Medication-related osteonecrosis of the jaw (MRONJ) is a refractory disease for which no established treatment currently exists. Surfactin, a biosurfactant produced by Bacillus subtilis, exhibits antimicrobial activity, anticancer effects, and anti-inflammatory properties, suggesting its potential medical applications. This study aimed to elucidate the ability of surfactin to modulate the immune response induced by lipopolysaccharide (LPS) derived from periodontal pathogens (Aggregatibacter actinomycetemcomitans), clarify the underlying molecular mechanisms, and explore its potential utility in the treatment of MRONJ. Reverse transcription quantitative polymerase chain reaction demonstrated that surfactin suppresses LPS-induced interleukin-6 (IL-6) expression and secretion in J774.1 cells in a concentration-dependent manner. Western blot analysis showed that surfactin inhibited activation of the JNK-c-Jun-AP-1 axis and the JAK\/STAT signaling pathways in J774.1 cells. The effects of surfactin administration were further evaluated in an in vivo MRONJ model. Co-treatment with surfactin significantly reduced the extent of LPS-induced bone necrosis. Overall, these findings suggest that surfactin suppresses LPS-induced IL-6 expression in macrophages and inhibits osteonecrosis induced by bisphosphonate preparations and LPS through negative regulation of the JNK-c-Jun-AP-1 axis and inhibition of the JAK\/STAT pathway. Hence, surfactin may represent a promising candidate for MRONJ management.<\/jats:p>","DOI":"10.3390\/ijms27031157","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T13:55:34Z","timestamp":1769176534000},"page":"1157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Basis of Surfactin-Induced Macrophage Modulation and Its Implications in Medication-Related Osteonecrosis of the Jaw Pathogenesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuki","family":"Kodama-Maruyama","sequence":"first","affiliation":[{"name":"Division of Infections and Molecular Biology, Department of Advanced Pathophysiological Science, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9426-184X","authenticated-orcid":false,"given":"Hiroki","family":"Tsurushima","sequence":"additional","affiliation":[{"name":"Division of Oral Medicine, Department of Oral and Maxillofacial Disease Control, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6259-6432","authenticated-orcid":false,"given":"Ayaka","family":"Koga","sequence":"additional","affiliation":[{"name":"Division of Infections and Molecular Biology, Department of Advanced Pathophysiological Science, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"},{"name":"Department of Health Sciences, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2615-6545","authenticated-orcid":false,"given":"Yoshie","family":"Nagai-Yoshioka","sequence":"additional","affiliation":[{"name":"Division of Infections and Molecular Biology, Department of Advanced Pathophysiological Science, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1152-3248","authenticated-orcid":false,"given":"Ryota","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Division of Infections and Molecular Biology, Department of Advanced Pathophysiological Science, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"},{"name":"Oral Medicine Innovation Center, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6586-2539","authenticated-orcid":false,"given":"Manabu","family":"Habu","sequence":"additional","affiliation":[{"name":"Division of Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Disease Control, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izumi","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Division of Oral Medicine, Department of Oral and Maxillofacial Disease Control, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-5683","authenticated-orcid":false,"given":"Wataru","family":"Ariyoshi","sequence":"additional","affiliation":[{"name":"Division of Infections and Molecular Biology, Department of Advanced Pathophysiological Science, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"},{"name":"Oral Medicine Innovation Center, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0278-2391(03)00720-1","article-title":"Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic","volume":"61","author":"Marx","year":"2003","journal-title":"J. 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