ArticleNature communications2024
Adipocyte associated glucocorticoid signaling regulates normal fibroblast function which is lost in inflammatory arthritis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies.Nature immunology · 2026Review
- Adipose-Joint Crosstalk in Obesity-Induced Osteoarthritis: Mechanisms, Biomarkers, and Translational Therapeutic Opportunities.Current rheumatology reports · 2026Review
- Targeting fibroblasts in immune mediated inflammatory diseases: a cellular basis for cure?Rheumatology (Oxford, England) · 2026Review
- Comparative Skin Transcriptome Analysis Identifies Candidate Genes Associated with Skin Responses in Hu Sheep Raised Under Different Regional Rearing Conditions.Animals : an open access journal from MDPI · 2026Article
- Metabolic Endotoxemia Amplifies Estrogen Signaling Through Stromal Crosstalk in Obesity-Associated Breast Cancer.International journal of molecular sciences · 2026Article
- Synovial transcriptional clusters link cartilage degeneration to cell-type-specific gene expression in knee osteoarthritis.bioRxiv : the preprint server for biology · 2026Article
- Novel insights into the biology of childhood arthritis- lessons learned from the synovium.Arthritis research & therapy · 2025Review
- Synovial matrix turnover controls immune cell spatial patterning in inflammation resolution.Molecular systems biology · 2025Article
- Screening and validation of diagnostic markers for keloids via bioinformatics analysis.Biochemistry and biophysics reports · 2025Article
- Adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis.The Journal of experimental medicine · 2025Article
- Fibroblasts in immune responses, inflammatory diseases and therapeutic implications.Nature reviews. Rheumatology · 2025Review
- Impaired adipocyte-mediated regulation of fibroblasts in inflammatory arthritis.Nature reviews. Rheumatology · 2025Article
- The Function of the TGFβ Signaling Pathway in Connective Tissue Diseases: From Biology to Clinical Application.Journal of inflammation research · 2025Review
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Authors and funding
18 authors.
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Abstract
Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Little is known about what regulates the homeostatic functions of fibroblasts. Here, we perform RNA sequencing and identify a gene expression program in healthy synovial fibroblasts characterized by enhanced fatty acid metabolism and lipid transport. We identify cortisol as the key driver of the healthy fibroblast phenotype and that depletion of adipocytes, which express high levels of Hsd11b1, results in loss of the healthy fibroblast phenotype in mouse synovium. Additionally, fibroblast-specific glucocorticoid receptor Nr3c1 deletion in vivo leads to worsened arthritis. Cortisol signaling in fibroblasts mitigates matrix remodeling induced by TNF and TGF-β1 in vitro, while stimulation with these cytokines represses cortisol signaling and adipogenesis. Together, these findings demonstrate the importance of adipocytes and cortisol signaling in driving the healthy synovial fibroblast state that is lost in disease.
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