{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:25:48Z","timestamp":1789442748577,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["GREWIS, 02NUK017A, GREWIS alpha 02NUK050A"],"award-info":[{"award-number":["GREWIS, 02NUK017A, GREWIS alpha 02NUK050A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiotherapy is a widely used treatment option for cancer patients as well as for patients with musculoskeletal disorders. Adipocytes, the dominant cell type of adipose tissue, are known to constitute an active part of the tumor microenvironment. Moreover, adipocytes support inflammatory processes and cartilage degradation in chronic inflammatory diseases, i.e., rheumatoid and osteoarthritis. Since the production of inflammatory factors is linked to their differentiation stages, we set out to explore the radiation response of pre-adipocytes that may influence their inflammatory potential and differentiation capacity. This is the first study investigating the effects of X-ray irradiation on the proliferation and differentiation capacity of human primary pre-adipocytes, in comparison to Simpson\u2013Golabi\u2013Behmel Syndrome (SGBS) pre-adipocytes, an often-used in vitro model of human primary pre-adipocytes. Our results demonstrate a dose-dependent reduction of the proliferation capacity for both cell strains, whereas the potential for differentiation was mostly unaffected by irradiation. The expression of markers of adipogenic development, such as transcription factors (PPAR\u03b3, C\/EBP\u03b1 and C\/EBP\u03b2), as well as the release of adipokines (visfatin, adiponectin and leptin) were not significantly changed upon irradiation. However, after irradiation with high X-ray doses, an increased lipid accumulation was observed, which suggests a radiation-induced response of adipocytes related to inflammation. Our results indicate that pre-adipocytes are radio-resistant, and it remains to be elucidated whether this holds true for the overall inflammatory response of adipocytes upon irradiation.<\/jats:p>","DOI":"10.3390\/ijms19092717","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T11:40:02Z","timestamp":1536666002000},"page":"2717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of X-ray Exposure on the Proliferation and Differentiation of Human Pre-Adipocytes"],"prefix":"10.3390","volume":"19","author":[{"given":"Kateryna","family":"Shreder","sequence":"first","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, 64291 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0968-1546","authenticated-orcid":false,"given":"Felicitas","family":"Rapp","sequence":"additional","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, 64291 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Tsoukala","sequence":"additional","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, 64291 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Rzeznik","sequence":"additional","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, 64291 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wabitsch","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Fischer-Posovszky","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, 89075 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Fournier","sequence":"additional","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, 64291 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3389\/fimmu.2013.00453","article-title":"Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing spondylitis. A comparative study","volume":"4","author":"Toussirot","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1210\/er.2005-0022","article-title":"Role of adipose tissue as an inflammatory organ in human diseases","volume":"27","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.endonu.2013.03.011","article-title":"Adipose tissue: Cell heterogeneity and functional diversity","volume":"61","year":"2014","journal-title":"Endocrinol. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/ar4422","article-title":"An emerging player in knee osteoarthritis: The infrapatellar fat pad","volume":"15","author":"Kloppenburg","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1016\/j.febslet.2005.05.031","article-title":"Adipose tissues as an ancestral immune organ: Site-specific change in obesity","volume":"579","author":"Cousin","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.7150\/jca.16884","article-title":"Obesity and cancer: The role of adipose tissue and adipo-cytokines-induced chronic inflammation","volume":"7","author":"Divella","year":"2016","journal-title":"J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1083\/jcb.201409063","article-title":"The cell biology of fat expansion","volume":"208","author":"Rutkowski","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.tips.2015.04.014","article-title":"Adipokines in health and disease","volume":"36","author":"Fasshauer","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2010.12.008","article-title":"NF-kB, Inflammation, and Metabolic Disease","volume":"13","author":"Baker","year":"2011","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.3390\/ijms15046184","article-title":"Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease","volume":"15","author":"Jung","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1161\/CIRCRESAHA.111.262493","article-title":"Adipose tissue biology and cardiomyopathy: Translational implications","volume":"111","author":"Turer","year":"2012","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/ajcn\/83.2.461S","article-title":"Obesity and the role of adipose tissue in inflammation and metabolism 1\u20134","volume":"83","author":"Greenberg","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1016\/j.bbalip.2013.02.010","article-title":"Adipose tissue and adipocytes supports tumorigenesis and metastasis","volume":"1831","author":"Nieman","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.cytogfr.2009.05.007","article-title":"Angiogenesis, adipokines and breast cancer","volume":"20","author":"Rose","year":"2009","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_15","first-page":"1","article-title":"Interactions between adipocytes and breast cancer cells ctimulate cytokine production and drive Src\/Sox2\/miR-302b\u2014Mediated malignant progression","volume":"76","author":"Pan","year":"2016","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"57622","DOI":"10.18632\/oncotarget.18038","article-title":"The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance","volume":"8","author":"Duong","year":"2017","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nrrheum.2016.49","article-title":"Adipokines in bone disease","volume":"12","author":"Neumann","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2169\/internalmedicine.50.4306","article-title":"Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis","volume":"50","author":"Yoshino","year":"2011","journal-title":"Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nrrheum.2011.107","article-title":"What\u2019s new in our understanding of the role of adipokines in rheumatic diseases?","volume":"7","author":"Conde","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"343746","DOI":"10.1155\/2014\/343746","article-title":"Adipokines, metabolic syndrome and rheumatic diseases","volume":"2014","author":"Abella","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4468","DOI":"10.4049\/jimmunol.176.7.4468","article-title":"The potential of adiponectin in driving arthritis","volume":"176","author":"Ehling","year":"2006","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.canlet.2015.04.010","article-title":"Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases","volume":"368","author":"Frey","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cui, J., Yang, G., Pan, Z., Zhao, Y., Liang, X., and Li, W. (2017). Hormetic response to low-dose radiation: Focus on the immune system and its clinical implications. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020280"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2353\/ajpath.2009.080505","article-title":"Adipose tissue sensitivity to radiation exposure","volume":"174","author":"Poglio","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3109\/09553002.2010.537429","article-title":"Ionising radiation triggers fat accumulation in white adipose tissue","volume":"87","author":"Jo","year":"2011","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000145784","article-title":"Human SGBS cells\u2014A unique tool for studies of human fat cell biology","volume":"1","author":"Newell","year":"2008","journal-title":"Obes. Facts"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ruiz-Ojeda, F.J., Ruperez, A.I., Gomez-Llorente, C., Gil, A., and Aguilera, C.M. (2016). Cell models and their application for studying adipogenic differentiation in relation to obesity: A review. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071040"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/sj.ijo.0801520","article-title":"Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation","volume":"25","author":"Wabitsch","year":"2001","journal-title":"Int. J. Obes."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nrm2066","article-title":"Adipocyte differentiation from the inside out","volume":"7","author":"Rosen","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/jcb.22598","article-title":"Cellular models for understanding adipogenesis, adipose dysfunction, and obesity","volume":"110","author":"Armani","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bbrc.2011.06.101","article-title":"Cancer-associated adipocytes promotes breast tumor radioresistance","volume":"411","author":"Bochet","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ncpendmet0456","article-title":"Mechanisms of Disease: Adipokines and breast cancer\u2014Endocrine and paracrine mechanisms that connect adiposity and breast cancer","volume":"3","author":"Buechler","year":"2007","journal-title":"Nat. Clin. Pract. Endocrin. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1259\/bjr.20150080","article-title":"Radiotherapy for non-malignant disorders: State of the art and update of the evidence-based practice guidelines","volume":"88","author":"Seegenschmiedt","year":"2015","journal-title":"Br. J. Radiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"519","DOI":"10.3389\/fimmu.2017.00519","article-title":"Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases","volume":"8","author":"Fournier","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"882","DOI":"10.3389\/fimmu.2017.00882","article-title":"Decrease of Markers related to Bone erosion in serum of Patients with Musculoskeletal Disorders after serial low-Dose radon spa Therapy","volume":"8","author":"Cucu","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3389\/fonc.2012.00058","article-title":"Radiation, inflammation, and immune responses in cancer","volume":"2","author":"Multhoff","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.ijrobp.2018.01.015","article-title":"The Radiation Resistance of Human Multipotent Mesenchymal Stromal Cells Is Independent of Their Tissue of Origin","volume":"100","author":"Xia","year":"2018","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1089\/scd.2009.0449","article-title":"Irradiation of Adult Human Dental Pulp Stem Cells Provokes Activation of p53, Cell Cycle Arrest and Senescence but not Apoptosis","volume":"19","author":"Muthna","year":"2010","journal-title":"Stem Cells Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ijrobp.2006.03.062","article-title":"The Sensitivity of human mesenchymal stem cells to ionizing radiation","volume":"66","author":"Chen","year":"2006","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.jcyt.2015.12.001","article-title":"Adipose mesenchymal stromal cells response to ionizing radiation","volume":"18","author":"Maria","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"19366","DOI":"10.18632\/oncotarget.4358","article-title":"Radio-resistant mesenchymal stem cells: Mechanisms of resistance and potential implications for the clinic","volume":"6","author":"Nicolay","year":"2015","journal-title":"Oncotarget"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13287-016-0378-0","article-title":"Serial changes in the proliferation and differentiation of adipose-derived stem cells after ionizing radiation","volume":"7","author":"Jeong","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1399-3046.2006.00663.x","article-title":"The effects of various irradiation doses on the growth and differentiation of marrow-derived human mesenchymal stromal cells","volume":"11","author":"Li","year":"2007","journal-title":"Pediatr. Transplant."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1001\/archotol.126.9.1124","article-title":"Radiation Effects on Osteoblasts In Vitro","volume":"126","author":"Gal","year":"2000","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1203\/00006450-199507000-00015","article-title":"Obesity after successful treatment of acute lymphoblastic leukemia in childhood","volume":"38","author":"Hahlen","year":"1995","journal-title":"Pediatr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1667\/RR1903.1","article-title":"Long-term effects of radiation exposure among adult survivors of Childhood cancer: Results from the CCSS","volume":"174","author":"Armstrong","year":"2011","journal-title":"Radiat. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1172\/JCI200319246","article-title":"Obesity is associated with macrophage accumulation","volume":"112","author":"Weisberg","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1152\/physrev.1998.78.3.783","article-title":"Understanding adipocyte differentiation","volume":"78","author":"Gregoire","year":"1998","journal-title":"Physiol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.18632\/oncotarget.2857","article-title":"Mesenchymal stem cells are resistant to carbon ion radiotherapy","volume":"6","author":"Nicolay","year":"2014","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1038\/s41598-017-04369-2","article-title":"SGBS cells as a model of human adipocyte browning: A comprehensive comparative study with primary human white subcutaneous adipocytes","volume":"7","author":"Yeo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/08916934.2017.1284819","article-title":"Modulation of the peripheral immune system after low-dose radon spa therapy: Detailed longitudinal immune monitoring of patients within the RAD-ON01 study","volume":"50","author":"Wunderlich","year":"2017","journal-title":"Autoimmunity"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1504\/IJLR.2010.037663","article-title":"Effect of combined Low-Dose Radon-and Hyperthermia Treatment (LDRnHT) of patients with ankylosing spondylitis on serum levels of cytokines and bone metabolism markers: A pilot study","volume":"7","author":"Moder","year":"2010","journal-title":"Int. J. Low Radiat."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2717\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:19:59Z","timestamp":1760195999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/9\/2717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,11]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["ijms19092717"],"URL":"https:\/\/doi.org\/10.3390\/ijms19092717","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,11]]}}}