{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:16:33Z","timestamp":1789895793435,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cataract, a leading cause of blindness, is characterised by lens opacification. Type 2 diabetes is associated with a two\u2010 to\u00a0fivefold higher prevalence of cataracts. The risk of cataract formation increases with the duration of diabetes and the severity of hyperglycaemia. Hydroxyapatite deposition is present in cataractous lenses that could be the consequence of osteogenic differentiation and calcification of lens epithelial cells (LECs). We hypothesised that hyperglycaemia might promote the osteogenic differentiation of human LECs (HuLECs). Osteogenic medium (OM) containing excess phosphate and calcium with normal (1\u2009g\/L) or high (4.5\u2009g\/L) glucose was used to induce HuLEC calcification. High glucose accelerated and intensified OM\u2010induced calcification of HuLECs, which was accompanied by hyperglycaemia\u2010induced upregulation of the osteogenic markers Runx2, Sox9, alkaline phosphatase\u00a0and osteocalcin, as well as nuclear translocation of Runx2. High glucose\u2010induced calcification was abolished in Runx2\u2010deficient HuLECs. Additionally, high glucose stabilised the regulatory alpha subunits of hypoxia\u2010inducible factor 1 (HIF\u20101), triggered nuclear translocation of HIF\u20101\u03b1\u00a0and increased the expression of HIF\u20101 target genes. Gene silencing of HIF\u20101\u03b1 or HIF\u20102\u03b1 attenuated hyperglycaemia\u2010induced calcification of HuLECs, while hypoxia mimetics (desferrioxamine, CoCl<jats:sub>2<\/jats:sub>) enhanced calcification of HuLECs under normal glucose conditions. Overall, this study suggests that high glucose promotes HuLEC calcification via Runx2 and the activation of the HIF\u20101 signalling pathway. These findings may provide new insights into the pathogenesis of diabetic cataracts, shedding light on potential factors for intervention to treat this sight\u2010threatening condition.<\/jats:p>","DOI":"10.1002\/jcp.31211","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T09:19:46Z","timestamp":1706865586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["High glucose promotes osteogenic differentiation of human lens epithelial cells through hypoxia\u2010inducible factor (HIF) activation"],"prefix":"10.1002","volume":"239","author":[{"given":"Haneen","family":"Ababneh","sequence":"first","affiliation":[{"name":"Research Centre for Molecular Medicine MTA\u2010DE Lend\u00fclet Vascular Pathophysiology Research Group, Faculty of Medicine University of Debrecen Debrecen Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3180-0559","authenticated-orcid":false,"given":"Enik\u0151","family":"Balogh","sequence":"additional","affiliation":[{"name":"Research Centre for Molecular Medicine MTA\u2010DE Lend\u00fclet Vascular Pathophysiology Research Group, Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vid M\u00e1t\u00e9","family":"Csiki","sequence":"additional","affiliation":[{"name":"Research Centre for Molecular Medicine MTA\u2010DE Lend\u00fclet Vascular Pathophysiology Research Group, Faculty of Medicine University of Debrecen Debrecen Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9ta","family":"Lente","sequence":"additional","affiliation":[{"name":"Research Centre for Molecular Medicine MTA\u2010DE Lend\u00fclet Vascular Pathophysiology Research Group, Faculty of Medicine University of Debrecen Debrecen Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Fenyvesi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Faculty of Pharmacy University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Research Centre for Molecular Medicine MTA\u2010DE Lend\u00fclet Vascular Pathophysiology Research Group, Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-7091","authenticated-orcid":false,"given":"Vikt\u00f3ria","family":"Jeney","sequence":"additional","affiliation":[{"name":"Research Centre for Molecular Medicine MTA\u2010DE Lend\u00fclet Vascular Pathophysiology Research Group, Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.13892"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312509"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.06.012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/8792"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)81446-S"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1164795"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.12.3226"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2005.01491.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl429"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.313791"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrs.2003.11.036"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108230"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01839-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1168339"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3073"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(86)90074-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2021.101279"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-015-2999-x"},{"key":"e_1_2_9_20_1","first-page":"1357","article-title":"Global and regional prevalence of age\u2010related cataract: A\u00a0comprehensive systematic review and meta\u2010analysis","volume":"34","author":"Hashemi H.","year":"2020","journal-title":"Eye (Basingstoke)"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2015.04.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(98)00280-3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(85)33877-0"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105776"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.1.23"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2021.1887272"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107872"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.3.16"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.03.020"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000084508"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106582"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.05.020"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(87)80011-8"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1076\/0928-6586(200006)721-ZFT103"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.267237"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.798053"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.08.016"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000059406.92165.31"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15277"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.42.6.801"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08362"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1015"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.31211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T10:26:58Z","timestamp":1717410418000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.31211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,2]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/jcp.31211"],"URL":"https:\/\/doi.org\/10.1002\/jcp.31211","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,2]]},"assertion":[{"value":"2023-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e31211"}}