Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls
Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting articular joints and skeletal muscle. To assess the role of cytokines upon muscle strength in RA, we developed an in vitro tissue-engineered human skeletal muscle model (myobundle). Myobundles were generated using primary...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07970-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850231384107384832 |
|---|---|
| author | Catherine E. Oliver Jonathan L. Carter James S. Hong Mingzhi Xu William E. Kraus Kim M. Huffman George A. Truskey |
| author_facet | Catherine E. Oliver Jonathan L. Carter James S. Hong Mingzhi Xu William E. Kraus Kim M. Huffman George A. Truskey |
| author_sort | Catherine E. Oliver |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting articular joints and skeletal muscle. To assess the role of cytokines upon muscle strength in RA, we developed an in vitro tissue-engineered human skeletal muscle model (myobundle). Myobundles were generated using primary skeletal muscle cells from the vastus lateralis muscle of RA patients and age-matched healthy controls. RA myobundles were more sensitive to 5 ng/mL IFN-γ, exhibiting reduced contractile force and altered contraction kinetics. Addition of IL-6 with or without IFN-γ led to a small but significant increase in striated fibers. Gene sets involved in the response to hypoxia, MTOR1 signaling, and the unfolded protein response were enriched in IFN-γ-treated RA myobundles, but not IFN-γ-treated controls. Tofacitinib increased contractile force and myosin heavy chain levels and restored PIM1 protein levels in RA myobundles treated with IFN-γ. Thus, in RA muscle, low levels of IFN-γ selectively increase gene pathways that reduce contractile force. |
| format | Article |
| id | doaj-art-c9b2ec6072f5458392ded2cb990e5cb5 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-c9b2ec6072f5458392ded2cb990e5cb52025-08-20T02:03:32ZengNature PortfolioCommunications Biology2399-36422025-04-018111410.1038/s42003-025-07970-8Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controlsCatherine E. Oliver0Jonathan L. Carter1James S. Hong2Mingzhi Xu3William E. Kraus4Kim M. Huffman5George A. Truskey6Department of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Biomedical Engineering, Duke UniversityDepartment of Medicine, Duke University School of MedicineDepartment of Medicine, Duke University School of MedicineDepartment of Biomedical Engineering, Duke UniversityAbstract Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting articular joints and skeletal muscle. To assess the role of cytokines upon muscle strength in RA, we developed an in vitro tissue-engineered human skeletal muscle model (myobundle). Myobundles were generated using primary skeletal muscle cells from the vastus lateralis muscle of RA patients and age-matched healthy controls. RA myobundles were more sensitive to 5 ng/mL IFN-γ, exhibiting reduced contractile force and altered contraction kinetics. Addition of IL-6 with or without IFN-γ led to a small but significant increase in striated fibers. Gene sets involved in the response to hypoxia, MTOR1 signaling, and the unfolded protein response were enriched in IFN-γ-treated RA myobundles, but not IFN-γ-treated controls. Tofacitinib increased contractile force and myosin heavy chain levels and restored PIM1 protein levels in RA myobundles treated with IFN-γ. Thus, in RA muscle, low levels of IFN-γ selectively increase gene pathways that reduce contractile force.https://doi.org/10.1038/s42003-025-07970-8 |
| spellingShingle | Catherine E. Oliver Jonathan L. Carter James S. Hong Mingzhi Xu William E. Kraus Kim M. Huffman George A. Truskey Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls Communications Biology |
| title | Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls |
| title_full | Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls |
| title_fullStr | Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls |
| title_full_unstemmed | Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls |
| title_short | Differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls |
| title_sort | differential response of tissue engineered skeletal muscle from rheumatoid arthritis patients and healthy controls |
| url | https://doi.org/10.1038/s42003-025-07970-8 |
| work_keys_str_mv | AT catherineeoliver differentialresponseoftissueengineeredskeletalmusclefromrheumatoidarthritispatientsandhealthycontrols AT jonathanlcarter differentialresponseoftissueengineeredskeletalmusclefromrheumatoidarthritispatientsandhealthycontrols AT jamesshong differentialresponseoftissueengineeredskeletalmusclefromrheumatoidarthritispatientsandhealthycontrols AT mingzhixu differentialresponseoftissueengineeredskeletalmusclefromrheumatoidarthritispatientsandhealthycontrols AT williamekraus differentialresponseoftissueengineeredskeletalmusclefromrheumatoidarthritispatientsandhealthycontrols AT kimmhuffman differentialresponseoftissueengineeredskeletalmusclefromrheumatoidarthritispatientsandhealthycontrols AT georgeatruskey differentialresponseoftissueengineeredskeletalmusclefromrheumatoidarthritispatientsandhealthycontrols |