{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T08:39:19Z","timestamp":1792399159116,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K08697"],"award-info":[{"award-number":["23K08697"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23tm0424225"],"award-info":[{"award-number":["JP23tm0424225"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aimed to elucidate the cellular and molecular mechanisms underlying knee osteoarthritis pathogenesis by analyzing chondrocyte populations and their spatial distribution using single\u2010cell RNA sequencing (scRNA\u2010seq). Knee cartilage cells underwent scRNA\u2010seq. Cellular clusters were identified via gene expression profiles and annotated using gene ontology analyses. Correlations between cluster proportions and patient background characteristics were evaluated. Differentiation trajectories were evaluated using pseudotime analysis. Differentially expressed genes between osteoarthritis and non\u2010osteoarthritis samples were identified, and their functional relevance was experimentally assessed. Cartilage stratification analysis was also performed. A total of 104,951 cells from 12 patients (9 osteoarthritis, 3 non\u2010osteoarthritis) were analyzed. Initially, 11 clusters were identified; three non\u2010chondrocytic clusters (mesenchymal stromal cell\u2010like cells, blood cells, fibroblasts) were identified and excluded from chondrocyte analysis. Eight chondrocyte subpopulations were annotated, including a novel stress\u2010responsive metabolic chondrocytes (MetabCs) associated with serum total cholesterol levels and linked to cholesterol metabolism and endoplasmic reticulum stress pathways. Correlation and trajectory analyses revealed two paths: one toward fibrocartilage chondrocytes (FCs) associated with aging and another toward MetabCs associated with osteoarthritis progression. Novel osteoarthritis\u2010related genes identified included chondroprotective\n                    <jats:italic>HILPDA<\/jats:italic>\n                    and destructive\n                    <jats:italic>AKR1C2<\/jats:italic>\n                    . Stratification analysis indicated that worn cartilage chondrocytes exhibited a hybrid phenotype, shifting toward upper\u2010zone features while retaining deep\u2010zone characteristics. In conclusion, a novel chondrocyte cluster was identified as implicated in osteoarthritis pathogenesis, where elevated serum cholesterol levels potentially increase endoplasmic reticulum stress response, promoting MetabC formation. Chondrocytes altered their phenotype in response to spatial distribution changes caused by cartilage thinning.\n                  <\/jats:p>","DOI":"10.1002\/jor.70279","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:43:46Z","timestamp":1790750626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Analysis of Cartilage\u2010Derived Cells Identifies Diverse Populations and a Cholesterol\/ER\u2010Stress Chondrocyte Subset in Knee OA"],"prefix":"10.1002","volume":"44","author":[{"given":"Yu","family":"Kobori","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Graduate School of Medicine, Kyoto University Kyoto 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