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Current therapies largely target downstream joint damage and fail to address underlying adipose\u2013joint pathological interactions. This review synthesises recent advances in understanding how systemic metabolic dysfunction, adipose tissue inflammation, and cellular heterogeneity revealed by single-cell analyses drive OA pathogenesis, and highlights emerging strategies targeting metabolic dysfunction and chronic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>We critically summarised human and experimental studies investigating the role of dysfunctional adipose depots, including visceral, subcutaneous, and infrapatellar fat, in joint degeneration. Mechanistic findings on adipokine signalling, immune activation, and metabolic stress were integrated with recent single-cell insights and therapeutic interventions addressing systemic metabolism and inflammation. Obesity promotes adipose tissue hypertrophy, hypoxia, and inflammatory adipokine secretion, which remodel systemic metabolism and alter the function of joint-resident cells. Crosstalk between adipocytes, macrophages, fibroblasts, and chondrocytes sustains chronic low-grade inflammation, oxidative stress, and extracellular matrix degradation. Single-cell analyses have revealed fibroblast and macrophage subsets that mediate depot-specific inflammatory circuits. Recent findings also point to metabolic modulators (GLP-1 receptor agonists), anti-adipokine agents, and regenerative strategies as promising interventions to modify disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Obesity-induced OA arises from multi-level metabolic and inflammatory crosstalk between adipose and joint tissues. Deciphering adipose\u2013joint crosstalk provides a foundation for precision therapies that address the upstream metabolic and inflammatory drivers of joint degeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11926-026-01229-9","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T08:18:11Z","timestamp":1786177091000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose\u2013Joint Crosstalk in Obesity\u2013Induced Osteoarthritis: Mechanisms, Biomarkers, and Translational Therapeutic Opportunities"],"prefix":"10.1007","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3954-1123","authenticated-orcid":false,"given":"Wei","family":"Hang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7473-6278","authenticated-orcid":false,"given":"Kathy","family":"Triantafilou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-1291","authenticated-orcid":false,"given":"You","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"1229_CR1","doi-asserted-by":"publisher","unstructured":"Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. 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After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.","order":3,"name":"Ethics","label":"Declaration of Generative AI and AI-Assisted Technologies in the Manuscript Preparation Process","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"We systematically searched PubMed databases for publications from January 2010 through December 2025 combining obesity and osteoarthritis terms, supplemented by targeted searches for specific mechanisms and advanced methodologies. Studies were prioritized based on mechanistic depth, methodological innovation (single-cell sequencing, spatial transcriptomics), and therapeutic relevance, emphasizing publications providing molecular or cellular insights into obesity-induced OA pathogenesis.","order":4,"name":"Ethics","label":"Literature Search and Study Selection","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"22"}}