{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:29:44Z","timestamp":1778891384090,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["19859"],"award-info":[{"award-number":["19859"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["20843"],"award-info":[{"award-number":["20843"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T008172\/1"],"award-info":[{"award-number":["MR\/T008172\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucocorticoids provide indispensable anti-inflammatory therapies. However, metabolic adverse effects including muscle wasting restrict their use. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1) modulates peripheral glucocorticoid responses through pre-receptor metabolism. This study investigates how 11\u03b2-HSD1 influences skeletal muscle responses to glucocorticoid therapy for chronic inflammation. We assessed human skeletal muscle biopsies from patients with rheumatoid arthritis and osteoarthritis for 11\u03b2-HSD1 activity ex vivo. Using the TNF-\u03b1-transgenic mouse model (TNF-tg) of chronic inflammation, we examined the effects of corticosterone treatment and 11\u03b2-HSD1 global knock-out (11\u03b2KO) on skeletal muscle, measuring anti-inflammatory gene expression, muscle weights, fiber size distribution, and catabolic pathways. Muscle 11\u03b2-HSD1 activity was elevated in patients with rheumatoid arthritis and correlated with inflammation markers. In murine skeletal muscle, glucocorticoid administration suppressed IL6 expression in TNF-tg mice but not in TNF-tg11\u03b2KO mice. TNF-tg mice exhibited reductions in muscle weight and fiber size with glucocorticoid therapy. In contrast, TNF-tg11\u03b2KO mice were protected against glucocorticoid-induced muscle atrophy. Glucocorticoid-mediated activation of catabolic mediators (FoxO1, Trim63) was also diminished in TNF-tg11\u03b2KO compared to TNF-tg mice. In summary, 11\u03b2-HSD1 knock-out prevents muscle atrophy associated with glucocorticoid therapy in a model of chronic inflammation. Targeting 11\u03b2-HSD1 may offer a strategy to refine the safety of glucocorticoids.<\/jats:p>","DOI":"10.3390\/ijms22157828","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T22:35:31Z","timestamp":1626993331000},"page":"7828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Global Deletion of 11\u03b2-HSD1 Prevents Muscle Wasting Associated with Glucocorticoid Therapy in Polyarthritis"],"prefix":"10.3390","volume":"22","author":[{"given":"Justine M.","family":"Webster","sequence":"first","affiliation":[{"name":"Institute for Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6211 LK Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6166-6784","authenticated-orcid":false,"given":"Michael S.","family":"Sagmeister","sequence":"additional","affiliation":[{"name":"Institute for Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chloe G.","family":"Fenton","sequence":"additional","affiliation":[{"name":"Institute for Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Research into Inflammatory Arthritis Centre Versus Arthritis, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex P.","family":"Seabright","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chiang","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-2310","authenticated-orcid":false,"given":"Simon W.","family":"Jones","sequence":"additional","affiliation":[{"name":"MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Filer","sequence":"additional","affiliation":[{"name":"Research into Inflammatory Arthritis Centre Versus Arthritis, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Cooper","sequence":"additional","affiliation":[{"name":"ANZAC Research Institute, The University of Sydney, Sydney, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth G.","family":"Lavery","sequence":"additional","affiliation":[{"name":"Institute for Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-1232","authenticated-orcid":false,"given":"Karim","family":"Raza","sequence":"additional","affiliation":[{"name":"Research into Inflammatory Arthritis Centre Versus Arthritis, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"MRC Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham B71 4HJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon","family":"Langen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6211 LK Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-6739","authenticated-orcid":false,"given":"Rowan S.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Institute for Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Research into Inflammatory Arthritis Centre Versus Arthritis, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Institute of Clinical Science, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","article-title":"The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights","volume":"335","author":"Coutinho","year":"2011","journal-title":"Mol. 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