{"title":"Adipose-Joint Crosstalk in Obesity-Induced Osteoarthritis: Mechanisms, Biomarkers, and Translational Therapeutic Opportunities.","authors":"Wei Hang, Kathy Triantafilou, You Zhou","doi":"10.1007/s11926-026-01229-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Obesity-induced osteoarthritis (OA) is emerging as a distinct metabolic phenotype fundamentally different from mechanically driven OA. Current therapies largely target downstream joint damage and fail to address underlying adipose-joint 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.</p><p><strong>Recent findings: </strong>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. Obesity-induced OA arises from multi-level metabolic and inflammatory crosstalk between adipose and joint tissues. Deciphering adipose-joint crosstalk provides a foundation for precision therapies that address the upstream metabolic and inflammatory drivers of joint degeneration.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452861/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Rheumatology Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11926-026-01229-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
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Abstract
Purpose of review: Obesity-induced osteoarthritis (OA) is emerging as a distinct metabolic phenotype fundamentally different from mechanically driven OA. Current therapies largely target downstream joint damage and fail to address underlying adipose-joint 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.
Recent findings: 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. Obesity-induced OA arises from multi-level metabolic and inflammatory crosstalk between adipose and joint tissues. Deciphering adipose-joint crosstalk provides a foundation for precision therapies that address the upstream metabolic and inflammatory drivers of joint degeneration.
期刊介绍：
This journal aims to review the most important, recently published research in the field of rheumatology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care and prevention of rheumatologic conditions.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas such as the many forms of arthritis, osteoporosis and metabolic bone disease, and systemic lupus erythematosus. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also occasionally provided.
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