{"doi":"10.1038/s42003-025-07970-8","title":"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 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, myosin heavy chain, and 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. Tissue-engineered skeletal muscle with myoblasts from rheumatoid arthritis patients is more sensitive to 5 ng/mL INF-g than controls, exhibiting reduced forces and altered gene expression, which is restored by treatment with a JAK pathway inhibitor.","journal":"Communications Biology","year":2025,"id":543679,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9247,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1433666,"name":"Jonathan L. Carter","orcid":"0000-0002-0191-9882","position":1,"is_corresponding":false},{"id":754539,"name":"James S Hong","orcid":"0000-0003-3452-8607","position":2,"is_corresponding":false},{"id":455267,"name":"Mingzhi Xu","orcid":"0009-0006-9626-1169","position":3,"is_corresponding":false},{"id":231464,"name":"William E. Kraus","orcid":"0000-0003-1930-9684","position":4,"is_corresponding":false},{"id":235342,"name":"Kim M. Huffman","orcid":"0000-0003-4708-4734","position":5,"is_corresponding":false},{"id":283946,"name":"George A. Truskey","orcid":"0000-0002-6885-4489","position":6,"is_corresponding":false},{"id":754538,"name":"Catherine E. Oliver","orcid":"0000-0003-3040-1326","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:53:08.338070Z","pmid":"40200033","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}