{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:59Z","timestamp":1787026559081,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Synovitis is a key driver of osteoarthritis (OA), characterized by a chronic inflammatory microenvironment. However, the contribution of immune-cell senescence to synovial pathology and its therapeutic potential remains poorly understood. This study aims to map the senescent immune landscape and identify actionable targets for OA therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell RNA dataset (GSE152805) of OA synovium was used to identify immune subsets with senescence-related transcriptional signatures and subset-specific gene signatures. These gene signatures served as machine-learning features to train and validate diagnostic models in a combine dataset of 4 OA transcriptomic datasets (GSE55235, GSE55457, GSE82107, GSE169077) using Random Forest, Support Vector Machine, Gradient Boosting Machine, and eXtreme Gradient Boosting. Immunofluorescence staining and Western blotting of human synovial tissues validated macrophage-associated markers. Pseudotime trajectory and cell\u2013cell communication analyses defined temporal dynamics and intercellular communication. Drug\u2013gene interaction analysis and molecular docking were performed to assess therapeutic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Macrophages, mast cells, and dendritic cells were identified as the immune populations with senescence-related transcriptional signatures. Pseudotime and communication analyses revealed a coordinated inflammatory continuum: macrophages initiated and sustained synovial inflammation, mast cells amplified intermediate inflammatory responses, and dendritic cells contributed to late-stage matrix remodeling. Machine-learning models identified hub biomarkers, with RHOB and PDK4 emerging as the macrophage-associated biomarkers with therapeutic potential. RHOB and PDK4 were markedly upregulated and colocalized with CD68\n                      <jats:sup>+<\/jats:sup>\n                      macrophages in OA synovium. Drug prediction suggested CHEMBL1797159 as a potential ligand for RHOB and dichloroacetate as a repurposable modulator of PDK4.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study characterizes the transcriptomic landscape of senescence-related features in the OA synovial microenvironment. We identify RHOB and PDK4 as key macrophage-associated therapeutic targets, providing novel insights for immunomodulatory strategies in OA treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1774722","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:13:45Z","timestamp":1776399225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune cells with senescence-related transcriptional signatures orchestrate the inflammatory continuum in osteoarthritis synovium: a single-cell and machine learning study"],"prefix":"10.3389","volume":"17","author":[{"given":"Chunrong","family":"He","sequence":"first","affiliation":[{"name":"Department of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University","place":["Chongqing, China"]},{"name":"Department of Orthopedic Surgery, The Second Affiliated 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