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Lincrna-Eps Regulates Iron Metabolism And Osteoclastogenesis Under Inflammatory Microenvironment

Year: 2025
Type: article
Abstract: To investigate the role and underlying mechanism of long intergenic noncoding RNA-erythroid prosurvival (lincRNA-EPS) in inflammatory osteoclastogenesis. Periodontitis was experimentally induced in 8-week-old male LincRNA-EPS-/- (KO) and wildtype (WT) C57BL/6 mice via lipopolysaccharide (LPS)-saturated silk ligature, following protocols approved by the Ethics Review Board of authors’ affiliation. After 14 days, alveolar bone resorption was quantified using micro-computed tomography. For in vitro osteoclastogenesis assays, bone marrow-derived macrophages (BMDMs) from both genotypes were stimulated with macrophage colony-stimulating factor, receptor activator for nuclear factor-κB ligand and LPS. Osteoclast formation was assessed through tartrate resistant acid phosphatase staining. Expression of osteoclast markers (Ctsk, Mmp9, Dcstamp, Nfatc1) was analyzed at mRNA and protein levels by real-time quantitative polymerase chain reaction (qPCR) and Western Blotting (WB). Transcriptomic profiling was conducted to identify the differentially expressed genes (DEGs) between WT and KO BMDMs during inflammatory osteoclast differentiation, and DEGs were verified through WB, immunofluorescence staining (IHC), qPCR, enzyme linked immunosorbent assay (ELISA). LincRNA-EPS deletion exacerbated LPS-induced alveolar bone resorption in vivo and upregulated osteoclast markers in vitro. Transcriptomics revealed dysregulated iron metabolism, osteoclastogenesis, IL-17 signaling, and ferroptosis pathways, represented by up-regulated gene Lcn2. LCN2 upregulation and iron metabolism changes were confirmed via IHC, WB and ELISA. This study delineates the regulatory role of lincRNA-EPS in inflammation-driven osteoclastogenesis and reveals its mediation of iron-metabolism, which helps understanding pathology of and developing targeted therapy for inflammatory bone disorders.
DOI: 10.1016/j.identj.2025.106084
Authors: Jin Wang, Yabing Wang, Jiansheng Su
Language: English
Open Access status: gold
Estimated APC paid: $2,550
OpenAlex ID: W7103887839
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