Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts
Tendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find pos...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/87092 |
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| author | Tino Stauber Greta Moschini Amro A Hussien Patrick Klaus Jaeger Katrien De Bock Jess G Snedeker |
| author_facet | Tino Stauber Greta Moschini Amro A Hussien Patrick Klaus Jaeger Katrien De Bock Jess G Snedeker |
| author_sort | Tino Stauber |
| collection | DOAJ |
| description | Tendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find positively enriched IL-6/JAK/STAT signaling alongside signatures of cell populations typically activated by IL-6 in other tissues. In human tendinopathic tendons, we also confirm the strong presence and co-localization of IL-6, IL-6R, and CD90, an established marker of reparative fibroblasts. To dissect the underlying causalities, we combine IL-6 knock-out mice with an explant-based assembloid model of tendon damage to successfully connect IL-6 signaling to reparative fibroblast activation and recruitment. Vice versa, we show that these reparative fibroblasts promote the development of tendinopathy hallmarks in the damaged explant upon IL-6 activation. We conclude that IL-6 activates tendon fibroblast populations which then initiate and deteriorate tendinopathy hallmarks. |
| format | Article |
| id | doaj-art-e5dc83c7517146bd8344b681a3aaed50 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-e5dc83c7517146bd8344b681a3aaed502025-02-07T14:14:44ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011210.7554/eLife.87092Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblastsTino Stauber0https://orcid.org/0000-0002-4060-5747Greta Moschini1Amro A Hussien2https://orcid.org/0000-0002-9324-9360Patrick Klaus Jaeger3Katrien De Bock4Jess G Snedeker5https://orcid.org/0000-0002-8115-0275Laboratory for Orthopedic Biomechanics, University Hospital Balgrist and ETH Zurich, Zurich, SwitzerlandLaboratory for Orthopedic Biomechanics, University Hospital Balgrist and ETH Zurich, Zurich, Switzerland; Laboratory of Exercise and Health Department of Health Sciences and Technology (D-HEST) ETH Zurich, Swiss Federal Institute of Technology, Zurich, SwitzerlandLaboratory for Orthopedic Biomechanics, University Hospital Balgrist and ETH Zurich, Zurich, SwitzerlandLaboratory for Orthopedic Biomechanics, University Hospital Balgrist and ETH Zurich, Zurich, SwitzerlandLaboratory of Exercise and Health Department of Health Sciences and Technology (D-HEST) ETH Zurich, Swiss Federal Institute of Technology, Zurich, SwitzerlandLaboratory for Orthopedic Biomechanics, University Hospital Balgrist and ETH Zurich, Zurich, SwitzerlandTendinopathies are debilitating diseases currently increasing in prevalence and associated costs. There is a need to deepen our understanding of the underlying cell signaling pathways to unlock effective treatments. In this work, we screen cell signaling pathways in human tendinopathies and find positively enriched IL-6/JAK/STAT signaling alongside signatures of cell populations typically activated by IL-6 in other tissues. In human tendinopathic tendons, we also confirm the strong presence and co-localization of IL-6, IL-6R, and CD90, an established marker of reparative fibroblasts. To dissect the underlying causalities, we combine IL-6 knock-out mice with an explant-based assembloid model of tendon damage to successfully connect IL-6 signaling to reparative fibroblast activation and recruitment. Vice versa, we show that these reparative fibroblasts promote the development of tendinopathy hallmarks in the damaged explant upon IL-6 activation. We conclude that IL-6 activates tendon fibroblast populations which then initiate and deteriorate tendinopathy hallmarks.https://elifesciences.org/articles/87092tendinopathyinterleukin-6tendonassembloidscleraxisfibroblast |
| spellingShingle | Tino Stauber Greta Moschini Amro A Hussien Patrick Klaus Jaeger Katrien De Bock Jess G Snedeker Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts eLife tendinopathy interleukin-6 tendon assembloid scleraxis fibroblast |
| title | Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts |
| title_full | Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts |
| title_fullStr | Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts |
| title_full_unstemmed | Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts |
| title_short | Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts |
| title_sort | il 6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblasts |
| topic | tendinopathy interleukin-6 tendon assembloid scleraxis fibroblast |
| url | https://elifesciences.org/articles/87092 |
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