{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:23:43Z","timestamp":1787729023452,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":236,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by progressive cartilage destruction, yet the heterogeneity of transitional chondrocyte states and their contributions to pathogenesis remain incompletely understood. In this study, we constructed a single\u2010cell transcriptomic atlas of human knee cartilage from 16 OA samples and 2 non\u2010OA normal donors. High\u2010resolution sub\u2010clustering of the prehypertrophic chondrocytes (preHTC) compartment revealed eight transcriptionally distinct subtypes, among which CRIP1\n                    <jats:sup>+<\/jats:sup>\n                    preHTC emerged as the most significantly expanded population in OA, particularly in weight\u2010bearing regions. Pseudotemporal trajectory inference and regulon analysis identified EGR3 as a candidate key regulator for CRIP1\n                    <jats:sup>+<\/jats:sup>\n                    preHTC. High\u2010dimensional weighted gene coexpression network analysis (hdWGCNA) demonstrated matrix\u2010remodeling and proteostasis\u2010stress transcriptional programs were highly active in CRIP1\n                    <jats:sup>+<\/jats:sup>\n                    preHTC. Cell\u2010cell communication analysis uncovered that CRIP1\n                    <jats:sup>+<\/jats:sup>\n                    preHTC acts as a central signaling hub in OA, with markedly enhanced FN1 signaling pathway. Spatial transcriptomics confirmed that CRIP1\n                    <jats:sup>+<\/jats:sup>\n                    preHTC co\u2010localizes with prefibroblasts (preFC) in pathological niches and interacts with other cells in the OA microenvironment. Finally, a machine\u2010learning\u2010based 10\u2010gene classifier (JUN, MCOLN3, RHOC, AKR7A2, HSPG2, AK4, B4GALT2, CLSTN1, LRRC41, and GADD45A) derived from CRIP1\n                    <jats:sup>+<\/jats:sup>\n                    preHTC\u2010associated hub genes accurately discriminated OA from normal tissues in two independent bulk RNA\u2010seq cohorts. Collectively, these findings suggest that CRIP1\n                    <jats:sup>+<\/jats:sup>\n                    preHTC may represent a pathogenic cell state in OA, provide a multi\u2010layered molecular framework that links a specific chondrocyte transitional subset to cartilage degradation, and offer a potentially useful gene signature for OA diagnosis.\n                  <\/jats:p>","DOI":"10.1155\/mi\/1194367","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:54:45Z","timestamp":1787727285000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Single\u2010Cell and Spatial Transcriptomics Identifies CRIP1\n                    <sup>+<\/sup>\n                    Prehypertrophic Chondrocytes as Inflammatory Hubs and a Valuable Diagnostic Biomarker for Osteoarthritis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0051-1126","authenticated-orcid":false,"given":"Zikang","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huwei","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chonghao","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00163-7"},{"key":"e_1_2_13_2_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0140-6736(24)02322-5","article-title":"Osteoarthritis","volume":"405","author":"Kloppenburg 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