{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:06:03Z","timestamp":1785240363891,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General Program of the Medical Development Foundation of Xi\u2019an Jiaotong University","award":["XJYG2025-SFJJ036"],"award-info":[{"award-number":["XJYG2025-SFJJ036"]}]},{"name":"IIT Clinical Research Fund of The Second Affiliated Hospital of Xi\u2019an Jiaotong University","award":["2025IIT-T01"],"award-info":[{"award-number":["2025IIT-T01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Frailty and osteoarthritis (OA) frequently coexist in older adults, yet the extent to which they share molecular programs across tissues remains unclear. We integrated bulk transcriptomics, peripheral immune and OA meniscal single-cell atlases, inferred cell\u2013cell communication, and an in vitro myeloid\u2013chondrocyte conditioned-medium model. Frailty-associated vastus lateralis and OA synovium shared a 16-gene program enriched for inflammatory and migratory processes, which was refined by protein\u2013protein interaction analysis into a 15-gene hub module (Hub-15). Donor-aware pseudobulk analysis showed coordinated Hub-15 upregulation in CD8 T, natural killer, B, and monocyte\/macrophage-like cells, with the highest scores in monocyte\/macrophage populations. In the meniscal atlas, donor-level analysis of 7 normal and 6 OA donors identified a 20.5 percentage point lower proportion of inflammatory\/stress cells and a 17.3 percentage point higher proportion of fibrochondrocyte-like cells in OA (both false discovery rate = 0.010), whereas state-specific Hub-15 differences were not significant after correction. Exploratory communication analysis nominated directionally consistent candidate myeloid-to-structural signaling axes, although none remained significant after multiple-testing correction. Conditioned medium from cytokine-primed THP-1 cells elicited inflammatory and matrix-catabolic responses in C28\/I2 cells. These findings identify a cross-tissue, leukocyte-shared, and myeloid-enriched inflammatory program that converges across independent frailty and OA cohorts, providing a hypothesis-generating framework for future mechanistic testing.<\/jats:p>","DOI":"10.3390\/ijms27156743","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:45:26Z","timestamp":1785239126000},"page":"6743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-Tissue Transcriptomic Convergence Identifies a Leuko-Cyte-Shared, Myeloid-Enriched Inflammatory Program in Frailty and Osteoarthritis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2111-5072","authenticated-orcid":false,"given":"Wang","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4158-8927","authenticated-orcid":false,"given":"Bingxiao","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7499-7507","authenticated-orcid":false,"given":"Zhihao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9039-2883","authenticated-orcid":false,"given":"Zenan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6484-1361","authenticated-orcid":false,"given":"Yisen","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0677-3052","authenticated-orcid":false,"given":"Zhikun","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlong","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-080X","authenticated-orcid":false,"given":"Zhibin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine and Pediatric Orthopaedics, The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an Jiaotong University, No. 157, Xiwu Road, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Osteoarthritis Collaborators (2023). 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