{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:53:56Z","timestamp":1780682036901,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIDCR\/NIH DE034067"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Osteoclasts, which are derived from myeloid precursors, are essential for physiologic bone remodeling but also mediate pathological bone loss in inflammatory diseases such as periodontitis and rheumatoid arthritis. Lysine-specific demethylase (LSD1\/KDM1A) is a histone demethylase that modulates the chromatin landscape via demethylation of H3K4me1\/2 and H3K9me1\/2, thereby regulating the expression of genes essential for deciding cell fate. We previously demonstrated that myeloid-specific deletion of LSD1 (LSD1LysM-Cre) disrupts osteoclast differentiation, leading to enhanced BV\/TV under physiological conditions. In this study, we show that LSD1LysM-Cre female mice are similarly resistant to inflammatory bone loss in both ligature-induced periodontitis and K\/BxN serum-transfer arthritis models. Bulk RNA-seq of mandibular-derived preosteoclasts from LSD1LysM-Cre mice with ligature-induced periodontitis revealed the upregulation of genes involved in inflammation, lipid metabolism, and immune response. Notably, LSD1 deletion blocked osteoclastogenesis even under TGF-\u03b2 and TNF co-stimulation, which is an alternative RANKL-independent differentiation pathway. Upregulation of Nlrp3, Hif1\u03b1, and Acod1 in LSD1LysM-Cre preosteoclasts suggests that LSD1 is essential for repressing inflammatory and metabolic programs that otherwise hinder osteoclast commitment. These findings establish LSD1 as a critical epigenetic gatekeeper integrating inflammatory and metabolic signals to regulate osteoclast differentiation and bone resorption. Therapeutic inhibition of LSD1 may selectively mitigate inflammatory bone loss while preserving physiological bone remodeling.<\/jats:p>","DOI":"10.3390\/cells14141111","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T07:56:14Z","timestamp":1753084574000},"page":"1111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Female Mice Lacking LSD1 in Myeloid Cells Are Resistant to Inflammatory Bone Loss"],"prefix":"10.3390","volume":"14","author":[{"given":"Kristina","family":"Astleford-Hopper","sequence":"first","affiliation":[{"name":"Oral Biology Graduate Program, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Saavedra","sequence":"additional","affiliation":[{"name":"Oral Biology Graduate Program, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA"},{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bittner-Eddy","sequence":"additional","affiliation":[{"name":"Division of Biological Science, Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Stein","sequence":"additional","affiliation":[{"name":"College of Biological Science, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2707-7561","authenticated-orcid":false,"given":"Jennifer","family":"Auger","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Allergy and Immunology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Clark","sequence":"additional","affiliation":[{"name":"Oral Biology Graduate Program, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-4307","authenticated-orcid":false,"given":"Juan E.","family":"Abrahante Llorens","sequence":"additional","affiliation":[{"name":"Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-3856","authenticated-orcid":false,"given":"Bryce A.","family":"Binstadt","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Allergy and Immunology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-3766","authenticated-orcid":false,"given":"Vivek","family":"Thumbigere-Math","sequence":"additional","affiliation":[{"name":"Division of Periodontology, Department of Advanced Oral Sciences, Therapeutics University of Maryland School of Dentistry, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-5030","authenticated-orcid":false,"given":"Kim C.","family":"Mansky","sequence":"additional","affiliation":[{"name":"Division of Orthodontics, Department of Developmental and Surgical Sciences, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.1210\/endo.139.10.6331","article-title":"A combination of osteoclast differentiation factor and macrophage-colony stimulating factor is sufficient for both human and mouse osteoclast formation in vitro","volume":"139","author":"Quinn","year":"1998","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41413-023-00257-w","article-title":"New insights into inflammatory osteoclast precursors as therapeutic targets for rheumatoid arthritis and periodontitis","volume":"11","author":"Hascoet","year":"2023","journal-title":"Bone Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1111\/1756-185X.13240","article-title":"Rheumatoid arthritis and periodontal disease: What are the similarities and differences?","volume":"20","author":"Li","year":"2017","journal-title":"Int. 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