{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T14:54:05Z","timestamp":1766588045995,"version":"3.37.3"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2017R1E1A1A01073021"],"award-info":[{"award-number":["2017R1E1A1A01073021"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2020R1C1C1014665"],"award-info":[{"award-number":["2020R1C1C1014665"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002630","name":"Ewha Womans University","doi-asserted-by":"publisher","award":["RP-Grant 2021"],"award-info":[{"award-number":["RP-Grant 2021"]}],"id":[{"id":"10.13039\/501100002630","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Obesity, which has become a major global health problem, involves a constitutive increase in adipocyte differentiation signaling. Previous studies show that mesenchymal stem cells (MSCs) induce weight loss and glycemic control. However, the mechanisms by which MSCs regulate adipocyte differentiation are not yet known. In this study, we investigated the effects of conditioned medium obtained from human tonsil-derived MSCs (T-MSC CM) on adipocyte differentiation. We found that T-MSC CM attenuated adipocyte differentiation from early stages via inhibiting glucocorticoid signaling. T-MSC CM also increased the phosphorylation of p38 mitogen-activated protein kinase and glucocorticoid receptors and decreased the subsequent nucleus translocation of glucocorticoid receptors. Chronic treatment of mice with synthetic glucocorticoids induced visceral and bone marrow adipose tissue expansion, but these effects were not observed in mice injected with T-MSC CM. Furthermore, T-MSC CM injection protected against reductions in blood platelet counts induced by chronic glucocorticoid treatment, and enhanced megakaryocyte differentiation was also observed. Collectively, these results demonstrate that T-MSC CM exerts inhibitory effects on adipocyte differentiation by regulating glucocorticoid signal transduction. These findings suggest that the therapeutic application of T-MSC CM could reduce obesity by preventing adipose tissue expansion.<\/jats:p>","DOI":"10.1371\/journal.pone.0266857","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T17:40:53Z","timestamp":1654105253000},"page":"e0266857","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Conditioned medium from human tonsil-derived mesenchymal stem cells inhibits glucocorticoid-induced adipocyte differentiation"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-9264","authenticated-orcid":true,"given":"Yu-Hee","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Ji","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung-Ah","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So-Youn","family":"Woo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung-Ha","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"issue":"9492","key":"pone.0266857.ref001","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/S0140-6736(05)67483-1","article-title":"Obesity","volume":"366","author":"DW Haslam","year":"2005","journal-title":"Lancet"},{"issue":"7","key":"pone.0266857.ref002","doi-asserted-by":"crossref","first-page":"161","DOI":"10.21037\/atm.2017.03.107","article-title":"Morbidity and mortality associated with obesity","volume":"5","author":"M Abdelaal","year":"2017","journal-title":"Ann Transl Med"},{"issue":"1","key":"pone.0266857.ref003","doi-asserted-by":"crossref","first-page":"e2568","DOI":"10.1038\/cddis.2016.308","article-title":"Human adipose stem cell differentiation is highly affected by cancer cells both in vitro and in vivo: implication for autologous fat grafting","volume":"8","author":"F Paino","year":"2017","journal-title":"Cell Death Dis"},{"issue":"6","key":"pone.0266857.ref004","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20061419","article-title":"Obesity-Altered Adipose Stem Cells Promote ER(+) Breast Cancer Metastasis through Estrogen Independent Pathways","volume":"20","author":"RA Sabol","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"52","key":"pone.0266857.ref005","doi-asserted-by":"crossref","first-page":"33295","DOI":"10.1073\/pnas.2005950117","article-title":"Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin","volume":"117","author":"Y Gao","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pone.0266857.ref006","doi-asserted-by":"crossref","first-page":"e004787","DOI":"10.1136\/bmjopen-2014-004787","article-title":"The future burden of obesity-related diseases in the 53 WHO European-Region countries and the impact of effective interventions: a modelling study","volume":"4","author":"L Webber","year":"2014","journal-title":"BMJ Open"},{"issue":"1\u20132","key":"pone.0266857.ref007","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cell.2013.12.012","article-title":"What we talk about when we talk about fat","volume":"156","author":"ED Rosen","year":"2014","journal-title":"Cell"},{"issue":"10","key":"pone.0266857.ref008","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1091\/mbc.e08-04-0420","article-title":"Glucocorticoid signaling defines a novel commitment state during adipogenesis in vitro","volume":"19","author":"C Pantoja","year":"2008","journal-title":"Mol Biol Cell"},{"issue":"6","key":"pone.0266857.ref009","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1530\/eje.0.1490561","article-title":"Computed tomography assessment of fat distribution in male and female patients with Cushing\u2019s syndrome","volume":"149","author":"AG Rockall","year":"2003","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"pone.0266857.ref010","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1507\/endocrj.52.623","article-title":"Insulin-induced lipohypertrophy: report of a case with histopathology","volume":"52","author":"J Fujikura","year":"2005","journal-title":"Endocr J"},{"key":"pone.0266857.ref011","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s13287-015-0201-3","article-title":"Adipose-derived mesenchymal stem cells improve glucose homeostasis in high-fat diet-induced obese mice","volume":"6","author":"M Cao","year":"2015","journal-title":"Stem Cell Res Ther"},{"issue":"4","key":"pone.0266857.ref012","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1507\/endocrj.EJ14-0584","article-title":"Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats","volume":"62","author":"J Hu","year":"2015","journal-title":"Endocr J"},{"issue":"1","key":"pone.0266857.ref013","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.bbrc.2016.12.125","article-title":"Adipose-derived mesenchymal stem cells ameliorate hyperglycemia through regulating hepatic glucose metabolism in type 2 diabetic rats","volume":"483","author":"M Xie","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"pone.0266857.ref014","article-title":"Administration of Tonsil-Derived Mesenchymal Stem Cells Improves Glucose Tolerance in High Fat Diet-Induced Diabetic Mice via Insulin-Like Growth Factor-Binding Protein 5-Mediated Endoplasmic Reticulum Stress Modulation","volume":"8","author":"Y Lee","year":"2019","journal-title":"Cells"},{"issue":"15","key":"pone.0266857.ref015","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1089\/scd.2016.0063","article-title":"Tonsil-Derived Mesenchymal Stem Cells Promote Bone Mineralization and Reduce Marrow and Visceral Adiposity in a Mouse Model of Senile Osteoporosis","volume":"25","author":"YH Kim","year":"2016","journal-title":"Stem Cells Dev"},{"issue":"5","key":"pone.0266857.ref016","doi-asserted-by":"crossref","first-page":"6170","DOI":"10.3892\/mmr.2017.7335","article-title":"Conditioned medium from tonsilderived mesenchymal stem cells promotes adiponectin production","volume":"16","author":"YH Kim","year":"2017","journal-title":"Mol Med Rep"},{"issue":"4","key":"pone.0266857.ref017","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1067\/mai.2002.122465","article-title":"p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma","volume":"109","author":"E Irusen","year":"2002","journal-title":"J Allergy Clin Immunol"},{"issue":"7","key":"pone.0266857.ref018","doi-asserted-by":"crossref","first-page":"e41582","DOI":"10.1371\/journal.pone.0041582","article-title":"Restoration of corticosteroid sensitivity by p38 mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma","volume":"7","author":"N Mercado","year":"2012","journal-title":"PLoS One"},{"issue":"7","key":"pone.0266857.ref019","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1002\/1529-0131(199907)42:7<1405::AID-ANR14>3.0.CO;2-W","article-title":"Fat conversion of femoral marrow in glucocorticoid-treated patients: a cross-sectional and longitudinal study with magnetic resonance imaging","volume":"42","author":"BC Vande Berg","year":"1999","journal-title":"Arthritis Rheum"},{"issue":"2","key":"pone.0266857.ref020","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1210\/en.2015-1477","article-title":"Expansion of Bone Marrow Adipose Tissue During Caloric Restriction Is Associated With Increased Circulating Glucocorticoids and Not With Hypoleptinemia","volume":"157","author":"WP Cawthorn","year":"2016","journal-title":"Endocrinology"},{"issue":"6","key":"pone.0266857.ref021","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/s11914-019-00554-6","article-title":"Endogenous Glucocorticoid Signaling in the Regulation of Bone and Marrow Adiposity: Lessons from Metabolism and Cross Talk in Other Tissues","volume":"17","author":"AK Sharma","year":"2019","journal-title":"Curr Osteoporos Rep"},{"issue":"7252","key":"pone.0266857.ref022","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nature08099","article-title":"Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment","volume":"460","author":"O Naveiras","year":"2009","journal-title":"Nature"},{"issue":"9","key":"pone.0266857.ref023","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.tips.2013.07.003","article-title":"Glucocorticoid receptor signaling in health and disease","volume":"34","author":"M Kadmiel","year":"2013","journal-title":"Trends Pharmacol Sci"},{"issue":"1","key":"pone.0266857.ref024","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0163-7258(02)00297-8","article-title":"Mechanisms involved in the side effects of glucocorticoids","volume":"96","author":"H Schacke","year":"2002","journal-title":"Pharmacol Ther"},{"key":"pone.0266857.ref025","doi-asserted-by":"crossref","first-page":"e2062","DOI":"10.1038\/cddis.2015.327","article-title":"Mesenchymal stem cells and immunomodulation: current status and future prospects","volume":"7","author":"F Gao","year":"2016","journal-title":"Cell Death Dis"},{"issue":"8","key":"pone.0266857.ref026","doi-asserted-by":"crossref","first-page":"506","DOI":"10.4252\/wjsc.v11.i8.506","article-title":"Tonsil-derived stem cells as a new source of adult stem cells","volume":"11","author":"KA Cho","year":"2019","journal-title":"World J Stem Cells"},{"issue":"3","key":"pone.0266857.ref027","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/rheumatology\/37.3.292","article-title":"The deleterious effects of low-dose corticosteroids on bone density in patients with polymyalgia rheumatica","volume":"37","author":"G Pearce","year":"1998","journal-title":"Br J Rheumatol"},{"issue":"6","key":"pone.0266857.ref028","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1378\/chest.116.6.1733","article-title":"Chronic glucocorticoid therapy-induced osteoporosis in patients with obstructive lung disease","volume":"116","author":"MF Goldstein","year":"1999","journal-title":"Chest"},{"issue":"8","key":"pone.0266857.ref029","first-page":"1620","article-title":"Potential value of vertebral proton MR spectroscopy in determining bone weakness","volume":"22","author":"D Schellinger","year":"2001","journal-title":"AJNR Am J Neuroradiol"},{"issue":"3","key":"pone.0266857.ref030","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1023\/A:1011513223894","article-title":"Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis","volume":"2","author":"J Justesen","year":"2001","journal-title":"Biogerontology"},{"issue":"4","key":"pone.0266857.ref031","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1182\/blood.V49.4.599.599","article-title":"Cell size and plamitate-1-14c turnover of rabbit marrow fat","volume":"49","author":"S Trubowitz","year":"1977","journal-title":"Blood"},{"issue":"6","key":"pone.0266857.ref032","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.bone.2009.02.022","article-title":"A study of bone marrow and subcutaneous fatty acid composition in subjects of varying bone mineral density","volume":"44","author":"JF Griffith","year":"2009","journal-title":"Bone"},{"issue":"1","key":"pone.0266857.ref033","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1038\/s41467-020-16878-2","article-title":"Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis","volume":"11","author":"KJ Suchacki","year":"2020","journal-title":"Nat Commun"},{"issue":"6","key":"pone.0266857.ref034","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/jbmr.3986","article-title":"Red and White Blood Cell Counts Are Associated With Bone Marrow Adipose Tissue, Bone Mineral Density, and Bone Microarchitecture in Premenopausal Women","volume":"35","author":"S Polineni","year":"2020","journal-title":"J Bone Miner Res"},{"issue":"1","key":"pone.0266857.ref035","article-title":"Conditioned Medium from Human Tonsil-Derived Mesenchymal Stem Cells Enhances Bone Marrow Engraftment via Endothelial Cell Restoration by Pleiotrophin","volume":"9","author":"YH Kim","year":"2020","journal-title":"Cells"},{"issue":"1","key":"pone.0266857.ref036","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1186\/s13287-021-02414-6","article-title":"Tonsil-derived mesenchymal stem cells enhance allogeneic bone marrow engraftment via collagen IV degradation","volume":"12","author":"HJ Lee","year":"2021","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"pone.0266857.ref037","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s13770-021-00401-9","article-title":"Promotion of Platelet Production by Co-Transplantation of Mesenchymal Stem Cells in Bone Marrow Transplantation","volume":"19","author":"YH Kim","year":"2022","journal-title":"Tissue Eng Regen Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266857","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T17:41:26Z","timestamp":1654105286000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266857"}},"subtitle":[],"editor":[{"given":"Gianpaolo","family":"Papaccio","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0266857","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2022,6,1]]}}}