{"doi":"10.3390/cells14141111","title":"Female Mice Lacking LSD1 in Myeloid Cells Are Resistant to Inflammatory Bone Loss","abstract":"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-β and TNF co-stimulation, which is an alternative RANKL-independent differentiation pathway. Upregulation of Nlrp3, Hif1α, 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.","journal":"Cells","year":2025,"id":545438,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":898640,"name":"Flávia Saavedra","orcid":"0000-0001-8623-8543","position":1,"is_corresponding":false},{"id":405359,"name":"Peter D. Bittner‐Eddy","orcid":"0009-0003-0429-0965","position":2,"is_corresponding":false},{"id":1436708,"name":"Clara Stein","orcid":null,"position":3,"is_corresponding":false},{"id":917982,"name":"Jennifer L. Auger","orcid":null,"position":4,"is_corresponding":false},{"id":1436709,"name":"Rachel Clark","orcid":null,"position":5,"is_corresponding":false},{"id":288568,"name":"Juan E. Abrahante","orcid":"0000-0002-9074-4307","position":6,"is_corresponding":false},{"id":470890,"name":"Bryce A. Binstadt","orcid":"0000-0003-3127-3856","position":7,"is_corresponding":false},{"id":483622,"name":"Vivek Thumbigere‐Math","orcid":"0000-0002-8279-3766","position":8,"is_corresponding":false},{"id":361558,"name":"Kim C. Mansky","orcid":"0000-0002-2826-5030","position":9,"is_corresponding":false},{"id":1436707,"name":"Kristina Astleford‐Hopper","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:53:23.001995Z","pmid":"40710364","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}