TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage
Objective: To further our understanding of the role of tumor necrosis factor (TNF)α on the inflammatory response in chondrocytes. Design: We explored the effects of TNFα on the transcriptome of epiphyseal chondrocytes from newborn C57BL/6 mice at the total and single cell (sc) resolution. Results: G...
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Elsevier
2024-12-01
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| Series: | Osteoarthritis and Cartilage Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665913124000955 |
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| author | Ernesto Canalis Lauren Schilling Emily Denker |
| author_facet | Ernesto Canalis Lauren Schilling Emily Denker |
| author_sort | Ernesto Canalis |
| collection | DOAJ |
| description | Objective: To further our understanding of the role of tumor necrosis factor (TNF)α on the inflammatory response in chondrocytes. Design: We explored the effects of TNFα on the transcriptome of epiphyseal chondrocytes from newborn C57BL/6 mice at the total and single cell (sc) resolution. Results: Gene set enrichment analysis of total RNA-Seq from TNFα-treated chondrocytes revealed enhanced response to biotic stimulus, defense and immune response and cytokine signaling and suppressed cartilage and skeletal morphogenesis and development. scRNA-Seq analyzed 14,239 cells and 24,320 genes and distinguished 16 cell clusters. The more prevalent ones were constituted by limb bud and chondrogenic cells and fibroblasts comprising ∼73 % of the cell population. Genes expressed by joint fibroblasts were detected in 5 clusters comprising ∼45 % of the cells isolated. Pseudotime trajectory finding revealed an association between fibroblast and chondrogenic clusters which was not modified by TNFα. TNFα decreased the total cells recovered by 18.5 % and the chondrogenic, limb bud and mesenchymal clusters by 32 %, 27 % and 7 %, respectively. TNFα had profound effects on the insulin-like growth factor (IGF) axis decreasing Igf1, Igf2 and Igfbp4 and inducing Igfbp3 and Igfbp5, explaining an inhibition of collagen biosynthesis, cartilage and skeletal morphogenesis. Ingenuity Pathway Analysis of scRNA-Seq data revealed that TNFα enhanced the osteoarthritis, rheumatoid arthritis, pathogen induced cytokine storm and interleukin 6 signaling pathways and suppressed fibroblast growth factor signaling. Conclusions: Epiphyseal chondrocytes are constituted by diverse cell populations distinctly regulated by TNFα to promote inflammation and suppression of matrix biosynthesis and growth. |
| format | Article |
| id | doaj-art-106197f5527e4491bbeb6c41005a7501 |
| institution | OA Journals |
| issn | 2665-9131 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Osteoarthritis and Cartilage Open |
| spelling | doaj-art-106197f5527e4491bbeb6c41005a75012025-08-20T02:05:28ZengElsevierOsteoarthritis and Cartilage Open2665-91312024-12-016410052810.1016/j.ocarto.2024.100528TNFα has differential effects on the transcriptome profile of selected populations in murine cartilageErnesto Canalis0Lauren Schilling1Emily Denker2Departments of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA; Departments of Medicine, UConn Health, Farmington, CT 06030, USA; UConn Musculoskeletal Institute, UConn Health, Farmington, CT 06030, USA; Corresponding author. Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030-4037, USA. Tel.: +860 679 7978; fax: +860 679 1474UConn Musculoskeletal Institute, UConn Health, Farmington, CT 06030, USAUConn Musculoskeletal Institute, UConn Health, Farmington, CT 06030, USAObjective: To further our understanding of the role of tumor necrosis factor (TNF)α on the inflammatory response in chondrocytes. Design: We explored the effects of TNFα on the transcriptome of epiphyseal chondrocytes from newborn C57BL/6 mice at the total and single cell (sc) resolution. Results: Gene set enrichment analysis of total RNA-Seq from TNFα-treated chondrocytes revealed enhanced response to biotic stimulus, defense and immune response and cytokine signaling and suppressed cartilage and skeletal morphogenesis and development. scRNA-Seq analyzed 14,239 cells and 24,320 genes and distinguished 16 cell clusters. The more prevalent ones were constituted by limb bud and chondrogenic cells and fibroblasts comprising ∼73 % of the cell population. Genes expressed by joint fibroblasts were detected in 5 clusters comprising ∼45 % of the cells isolated. Pseudotime trajectory finding revealed an association between fibroblast and chondrogenic clusters which was not modified by TNFα. TNFα decreased the total cells recovered by 18.5 % and the chondrogenic, limb bud and mesenchymal clusters by 32 %, 27 % and 7 %, respectively. TNFα had profound effects on the insulin-like growth factor (IGF) axis decreasing Igf1, Igf2 and Igfbp4 and inducing Igfbp3 and Igfbp5, explaining an inhibition of collagen biosynthesis, cartilage and skeletal morphogenesis. Ingenuity Pathway Analysis of scRNA-Seq data revealed that TNFα enhanced the osteoarthritis, rheumatoid arthritis, pathogen induced cytokine storm and interleukin 6 signaling pathways and suppressed fibroblast growth factor signaling. Conclusions: Epiphyseal chondrocytes are constituted by diverse cell populations distinctly regulated by TNFα to promote inflammation and suppression of matrix biosynthesis and growth.http://www.sciencedirect.com/science/article/pii/S2665913124000955TNFαChondrocytesInflammationTranscriptomeIGF1IGF2 |
| spellingShingle | Ernesto Canalis Lauren Schilling Emily Denker TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage Osteoarthritis and Cartilage Open TNFα Chondrocytes Inflammation Transcriptome IGF1 IGF2 |
| title | TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage |
| title_full | TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage |
| title_fullStr | TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage |
| title_full_unstemmed | TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage |
| title_short | TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage |
| title_sort | tnfα has differential effects on the transcriptome profile of selected populations in murine cartilage |
| topic | TNFα Chondrocytes Inflammation Transcriptome IGF1 IGF2 |
| url | http://www.sciencedirect.com/science/article/pii/S2665913124000955 |
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