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Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 (IL-1) disrupted circadian rhythms and degraded the cartilage matrix. All three inflammation-resistant approaches showed protection against IL-1\u2013induced degradation and loss of circadian rhythms. These synthetic gene circuits reveal a unique approach to support daily rhythms in cartilage and provide a strategy for creating cell-based therapies to preserve the circadian clock.<\/jats:p>","DOI":"10.1126\/sciadv.abj8892","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T13:57:46Z","timestamp":1653487066000},"source":"Crossref","is-referenced-by-count":39,"title":["Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1\u2013induced inflammation"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1968-3636","authenticated-orcid":true,"given":"Lara","family":"Pferdehirt","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA."},{"name":"Shriners Hospitals for Children\u2013St. Louis, St. Louis, MO 63110, USA."},{"name":"Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA."},{"name":"Department of Biomedical Engineering, Washington University, St. Louis, MO 63105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3283-3958","authenticated-orcid":true,"given":"Anna R.","family":"Damato","sequence":"additional","affiliation":[{"name":"Department of Biology, Washington University, St. Louis, MO 63130, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3152-1127","authenticated-orcid":true,"given":"Michal","family":"Dudek","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Cell Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-8336","authenticated-orcid":true,"given":"Qing-Jun","family":"Meng","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Cell Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-5174","authenticated-orcid":true,"given":"Erik D.","family":"Herzog","sequence":"additional","affiliation":[{"name":"Department of Biology, Washington University, St. Louis, MO 63130, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-0330","authenticated-orcid":true,"given":"Farshid","family":"Guilak","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA."},{"name":"Shriners Hospitals for Children\u2013St. Louis, St. Louis, MO 63110, USA."},{"name":"Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA."},{"name":"Department of Biomedical Engineering, Washington University, St. Louis, MO 63105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1177"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2430"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1766"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20140700"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308709101"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0179-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.01.048"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2019.07.008"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/0748730416662748"},{"key":"e_1_3_3_11_2","first-page":"66","article-title":"Biomechanics of cartilage","author":"Mansour J. 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