{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:47:54Z","timestamp":1786632474293,"version":"build-2736575974"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"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. Med."],"abstract":"<jats:p>Ankle osteoarthritis (OA) is commonly staged by pain, deformity, and radiographic joint-space loss, but this morphology-first view leaves much of its clinical heterogeneity unexplained. An ankle-specific precision framework is biologically and technically plausible because ankle OA is strongly enriched for post-traumatic mechanisms, has cartilage and synovial biology that differs from knee OA, and can be measured with weight-bearing structural and digital functional tools. Comparative cartilage studies show joint-dependent differences in catabolic susceptibility, matrix synthesis, transport, cell-matrix organization, and injury response. Human synovial-fluid and synovial-transcriptomic studies identify local inflammatory, remodeling, and WNT-related signals, while weight-bearing computed tomography (WBCT), automated three-dimensional alignment metrics, distance maps, gait analysis, plantar pressure, center of pressure (COP), and ankle-specific activity monitoring quantify structural and functional load signatures. This Mini Review integrates these data into four provisional, non-mutually-exclusive baseline research phenotypes: inflammatory-dominant, malalignment-dominant, post-traumatic or instability-dominant, and end-stage structural collapse. Post-surgical recovery is treated separately as a longitudinal response trajectory rather than a fifth baseline phenotype. The evidence is comparatively mature for ankle-knee cartilage differences, promising but preliminary for synovial, three-dimensional structural, and laboratory functional signatures, and exploratory for center-of-pressure recovery and wearable trajectories. A validation-ready pathway is proposed around a defined minimum same-patient dataset, serial measurement, a 24-month ankle-specific patient-reported outcome, explicit minimal-important-difference rules, trajectory modeling, calibrated prediction, and external evaluation. The framework is intended to organize prospective cohorts and treatment-response questions; it is not a validated clinical classification or automated treatment selector.<\/jats:p>","DOI":"10.3389\/fmed.2026.1931266","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:00:21Z","timestamp":1786629621000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular-biomechanical phenotyping of ankle osteoarthritis: from synovial biomarkers to weight-bearing digital signatures"],"prefix":"10.3389","volume":"13","author":[{"given":"Xueqing","family":"Han","sequence":"first","affiliation":[{"name":"Department of Hand and Foot Surgery, Neijiang Hospital of Traditional Chinese Medicine","place":["Neijiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Hand and Foot Surgery, 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