{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:31:38Z","timestamp":1786609898598,"version":"build-2736575974"},"reference-count":64,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>Knee osteoarthritis (KOA) is a heterogeneous whole-joint disorder in which mechanical loading, aging, metabolic stress, synovitis, microvascular dysfunction, matrix injury, subchondral remodeling, pain-related neurovascular change, and impaired repair interact over time. The infrapatellar fat pad (IFP) is increasingly recognized as an active synovio-adipose tissue, yet IFP inflammation, lipid disturbance, hypoxia, angiogenesis, matrix catabolism, and subchondral change are often considered parallel abnormalities rather than as a spatially organized propagation process. This Perspective proposes an IFP-centered spatial lipid-barrier coupling framework for a biologically enriched KOA subset. The central claim is not that lipid quantity alone drives KOA, but that lipid-derived signals become mechanistically meaningful when they appear in vulnerable barrier-defined spaces and co-localize with permeability injury, hypoxia, inflammatory execution, oxidative-matrix injury, or impaired repair. In this model, lipid-spatial mislocalization is a candidate threshold event, lipid-cytokine-hypoxia-barrier coupling is the progression engine, and barrier-defined propagation links the IFP, synovium, synovial cavity, cartilage matrix, osteochondral interface, and subchondral marrow-adipose compartment. Current evidence supports active IFP biology, IFP-synovium communication, circulation-to-joint-fluid access, multi-compartment lipid disturbance, HIF\/VEGF and FFA-NOX\/ROS pathways, and subchondral marrow involvement. However, source-resolved spatial co-localization and temporal ordering remain unproven. The framework should therefore be retained only if a reproducible lipid-barrier signature predicts progression, pain biology, or treatment response beyond synovitis, body mass index, malalignment, bone marrow lesions, and radiographic severity.<\/jats:p>","DOI":"10.1177\/1759720x261462643","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T07:08:37Z","timestamp":1786432117000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial lipid-barrier coupling in knee osteoarthritis: a mechanism-based perspective centered on the infrapatellar fat pad"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2661-0176","authenticated-orcid":false,"given":"Yuwu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Guangyuan Central Hospital, Guangyuan 628000, 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