{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:28:06Z","timestamp":1790126886467,"version":"4.0.1"},"reference-count":56,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92368201"],"award-info":[{"award-number":["92368201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81991514"],"award-info":[{"award-number":["81991514"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970577"],"award-info":[{"award-number":["81970577"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2021YFA1201404"],"award-info":[{"award-number":["2021YFA1201404"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Research"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>\n            Metal wear particles generated by the movement of joint prostheses inevitably lead to aseptic osteolytic damage and ultimately prosthesis loosening, which are aggravated by various types of regulated cell death of bone. Nevertheless, the exact cellular nature and regulatory network underlying osteoferroptosis are poorly understood. Here, we report that titanium particles (TP) induced severe peri-implant osteolysis and ferroptotic changes with concomitant transcriptional repression of a key anti-ferroptosis factor, GPX4, in a mouse model of calvarial osteolysis. GPX4 repression was accompanied by an increase in DNA methyltransferases (DNMTs) 1\/3a\/3b and hypermethylation of the\n            <jats:italic>Gpx4<\/jats:italic>\n            promoter, which were partly mediated by the transcriptional regulator\/co-repressor KLF5 and NCoR. Conversely, treatment with SGI-1027, a DNMT-specific inhibitor, resulted in marked reversal of\n            <jats:italic>Gpx4<\/jats:italic>\n            promoter hypermethylation and GPX4 repression, as well as improvement in ferroptotic osteolysis to a similar extent as with a ferroptosis inhibitor, liproxstatin-1. This suggests that epigenetic GPX4 repression and ferroptosis caused by the increase of DNMT1\/3a\/3b have a causal influence on TP-induced osteolysis. In cultured primary osteoblasts and osteoclasts, GPX4 repression and ferroptotic changes were observed primarily in osteoblasts that were alleviated by SGI-1027 in a GPX4 inactivation-sensitive manner. Furthermore, we developed a mouse strain with\n            <jats:italic>Gpx4<\/jats:italic>\n            haplodeficiency in osteoblasts (\n            <jats:italic>Gpx4<\/jats:italic>\n            <jats:sup>Ob+\/\u2212<\/jats:sup>\n            ) that exhibited worsened ferroptotic osteolysis in control and TP-treated calvaria and largely abolished the anti-ferroptosis and osteoprotective effects of SGI-1027. Taken together, our results demonstrate that DNMT1\/3a\/3b elevation, resulting GPX4 repression, and osteoblastic ferroptosis form a critical epigenetic pathway that significantly contributes to TP-induced osteolysis, and that targeting DNMT aberration and the associated osteoferroptosis could be a potential strategy to prevent or slow down prosthesis-related osteolytic complications.\n          <\/jats:p>","DOI":"10.34133\/research.0457","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T10:18:28Z","timestamp":1722421108000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":13,"title":["DNA Methylation-Mediated GPX4 Transcriptional Repression and Osteoblast Ferroptosis Promote Titanium Particle-Induced Osteolysis"],"prefix":"10.34133","volume":"7","author":[{"given":"Jian","family":"Dong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, \rAffiliated Hospital of Medical School, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binjia","family":"Ruan","sequence":"additional","affiliation":[{"name":"Nanjing University Medical School, JiangsuKey Lab of Molecular Medicine, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nanjing University Medical School, JiangsuKey Lab of Molecular Medicine, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Wei","sequence":"additional","affiliation":[{"name":"Nanjing University Medical School, JiangsuKey Lab of Molecular Medicine, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuling","family":"Li","sequence":"additional","affiliation":[{"name":"Nanjing University Medical School, JiangsuKey Lab of Molecular Medicine, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neng","family":"Tang","sequence":"additional","affiliation":[{"name":"Nanjing University Medical School, JiangsuKey Lab of Molecular Medicine, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Nanjing University Medical School, JiangsuKey Lab of Molecular Medicine, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, \rAffiliated Hospital of Medical School, Nanjing University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6209-3482","authenticated-orcid":true,"given":"Wangsen","family":"Cao","sequence":"additional","affiliation":[{"name":"Nanjing University Medical School, JiangsuKey Lab of Molecular Medicine, Nanjing, China."},{"name":"Yancheng Medical Research Center, Yancheng First People\u2019s Hospital, \rAffiliated Hospital of Nanjing University Medical School, Yancheng, China."},{"name":"Yangzhou Precision Research Institute of Kidney Disease, Department of Nephrology, Northern Jiangsu People\u2019s Hospital, Yangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207593"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/185150","article-title":"The pathology of orthopedic implant failure is mediated by innate immune system cytokines","volume":"2014","author":"Landgraeber S","year":"2014","unstructured":"Landgraeber S, Jager M, Jacobs JJ, Hallab NJ. The pathology of orthopedic implant failure is mediated by innate immune system cytokines. Mediat Inflamm. 2014;2014: Article 185150.","journal-title":"Mediat Inflamm"},{"issue":"12","key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.3390\/jcm8122091","article-title":"Periprosthetic osteolysis: Mechanisms, prevention and treatment","volume":"8","author":"Goodman SB","year":"2019","unstructured":"Goodman SB, Gallo J. Periprosthetic osteolysis: Mechanisms, prevention and treatment. J Clin Med. 2019;8(12):2091.","journal-title":"J Clin Med"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/01.blo.0000238813.95035.1b","article-title":"The cellular and molecular biology of periprosthetic osteolysis","volume":"454","author":"Purdue PE","year":"2007","unstructured":"Purdue PE, Koulouvaris P, Potter HG, Nestor BJ, Sculco TP. The cellular and molecular biology of periprosthetic osteolysis. Clin Orthop Relat Res. 2007;454:251\u2013261.","journal-title":"Clin Orthop Relat Res"},{"issue":"10","key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.molmed.2009.08.004","article-title":"Oxidative stress in bone remodelling and disease","volume":"15","author":"Wauquier F","year":"2009","unstructured":"Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y. Oxidative stress in bone remodelling and disease. Trends Mol Med. 2009;15(10):468\u2013477.","journal-title":"Trends Mol Med"},{"issue":"5","key":"e_1_3_3_7_2","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1002\/jbm.b.34546","article-title":"Reactive oxygen\/nitrogen species (ROS\/RNS) and oxidative stress in arthroplasty","volume":"108","author":"Hameister R","year":"2020","unstructured":"Hameister R, Kaur C, Dheen ST, Lohmann CH, Singh G. Reactive oxygen\/nitrogen species (ROS\/RNS) and oxidative stress in arthroplasty. J Biomed Mater Res B Appl Biomater. 2020;108(5):2073\u20132087.","journal-title":"J Biomed Mater Res B Appl Biomater"},{"issue":"7","key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3390\/nu8070423","article-title":"Avenanthramides prevent osteoblast and osteocyte apoptosis and induce osteoclast apoptosis in\u00a0vitro in an Nrf2-independent manner","volume":"8","author":"Pellegrini G","year":"2016","unstructured":"Pellegrini G, Morales C, Wallace T, Plotkin L, Bellido T. Avenanthramides prevent osteoblast and osteocyte apoptosis and induce osteoclast apoptosis in\u00a0vitro in an Nrf2-independent manner. Nutrients. 2016;8(7):423.","journal-title":"Nutrients"},{"issue":"1","key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15280\/jlm.2015.5.1.1","article-title":"Biological role of anti-aging protein Klotho","volume":"5","author":"Kim JH","year":"2015","unstructured":"Kim JH, Hwang KH, Park KS, Kong ID, Cha SK. Biological role of anti-aging protein Klotho. J Lifestyle Med. 2015;5(1):1\u20136.","journal-title":"J Lifestyle Med"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.34133\/research.0086"},{"issue":"12","key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.3390\/ijms17122045","article-title":"Cell death in chondrocytes, osteoblasts, and osteocytes","volume":"17","author":"Komori T","year":"2016","unstructured":"Komori T. Cell death in chondrocytes, osteoblasts, and osteocytes. Int J Mol Sci. 2016;17(12):2045.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"e_1_3_3_12_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12964-021-00799-8","article-title":"Regulated cell death: Discovery, features and implications for neurodegenerative diseases","volume":"19","author":"Cui J","year":"2021","unstructured":"Cui J, Zhao S, Li Y, Zhang D, Wang B, Xie J, Wang J. Regulated cell death: Discovery, features and implications for neurodegenerative diseases. Cell Commun Signal. 2021;19(1):120.","journal-title":"Cell Commun Signal"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8"},{"issue":"3","key":"e_1_3_3_14_2","doi-asserted-by":"crossref","first-page":"6163","DOI":"10.1080\/21655979.2022.2042143","article-title":"Ferrostatin-1 alleviates cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis","volume":"13","author":"Zhang W","year":"2022","unstructured":"Zhang W, Wang C, Zhu W, Liu F, Liu Y. Ferrostatin-1 alleviates cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis. Bioengineered. 2022;13(3):6163\u20136172.","journal-title":"Bioengineered"},{"issue":"1","key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12951-020-00700-8","article-title":"Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death","volume":"18","author":"Liu Y","year":"2020","unstructured":"Liu Y, Zhu W, Ni D, Zhou Z, Gu J-H, Zhang W, Sun H, Liu F. Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death. J Nanobiotechnol. 2020;18(1):141.","journal-title":"J Nanobiotechnol"},{"issue":"12","key":"e_1_3_3_16_2","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13142","article-title":"CoCrMo-nanoparticles induced peri-implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2-ARE signalling pathway","volume":"54","author":"Xu Y","year":"2021","unstructured":"Xu Y, Sang W, Zhong Y, Xue S, Yang M, Wang C, Lu H, Huan R, Mao X, Zhu L, et al. CoCrMo-nanoparticles induced peri-implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2-ARE signalling pathway. Cell Prolif. 2021;54(12): Article e13142.","journal-title":"Cell Prolif"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev-cancerbio-030518-055844","article-title":"The hallmarks of ferroptosis","volume":"3","author":"Dixonl SJ","year":"2019","unstructured":"Dixonl SJ, Stockwell BR. The hallmarks of ferroptosis. Annu Rev Cancer Biol. 2019;3:35\u201354.","journal-title":"Annu Rev Cancer Biol"},{"issue":"2","key":"e_1_3_3_18_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell BR","year":"2017","unstructured":"Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gasc\u00f3n S, Hatzios SK, Kagan VE, et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273\u2013285.","journal-title":"Cell"},{"issue":"3","key":"e_1_3_3_19_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbcan.2023.188890","article-title":"GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment","volume":"1878","author":"Liu Y","year":"2023","unstructured":"Liu Y, Wan Y, Jiang Y, Zhang L, Cheng W. GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment. Biochim Biophys Acta Rev Cancer. 2023;1878(3): Article 188890.","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031500"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3389\/fgene.2016.00115","article-title":"Modifiers and readers of DNA modifications and their impact on genome structure, expression, and stability in disease","volume":"7","author":"Ludwig AK","year":"2016","unstructured":"Ludwig AK, Zhang P, Cardoso MC. Modifiers and readers of DNA modifications and their impact on genome structure, expression, and stability in disease. Front Genet. 2016;7:115.","journal-title":"Front Genet"},{"issue":"1","key":"e_1_3_3_22_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore LD","year":"2012","unstructured":"Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2012;38(1):23\u201338.","journal-title":"Neuropsychopharmacology"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.freeradbiomed.2020.08.029","article-title":"Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4","volume":"160","author":"Xuyang Z","year":"2020","unstructured":"Xuyang Z, Zhaobo H, Ziang X, Yilei C, Zeyu Z, Xiao\u2019an W, Bao H, Zhi S, Junhui L, Shunwu F, et al. Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4. Free Radic Biol Med. 2020;160:552\u2013565.","journal-title":"Free Radic Biol Med"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac069"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2022.121742","article-title":"NRF2 is a critical regulator and therapeutic target of metal implant particle-incurred bone damage","volume":"288","author":"Dong J","year":"2022","unstructured":"Dong J, Zhang L, Ruan B, Lv Z, Wang H, Wang Y, Jiang Q, Cao W. NRF2 is a critical regulator and therapeutic target of metal implant particle-incurred bone damage. Biomaterials. 2022;288: Article 121742.","journal-title":"Biomaterials"},{"issue":"12","key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Friedmann Angeli JP","year":"2014","unstructured":"Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, Herbach N, Aichler M, Walch A, Eggenhofer E, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014;16(12):1180\u20131191.","journal-title":"Nat Cell Biol"},{"issue":"5","key":"e_1_3_3_27_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2006203","article-title":"Unsolved mysteries: How does lipid peroxidation cause ferroptosis?","volume":"16","author":"Feng H","year":"2018","unstructured":"Feng H, Stockwell BR. Unsolved mysteries: How does lipid peroxidation cause ferroptosis? PLOS Biol. 2018;16(5): Article e2006203.","journal-title":"PLOS Biol"},{"key":"e_1_3_3_28_2","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.biopha.2016.09.100","article-title":"KLF5 overexpression attenuates cardiomyocyte inflammation induced by oxygen-glucose deprivation\/reperfusion through the PPAR\u03b3\/PGC-1\u03b1\/TNF-\u03b1 signaling pathway","volume":"84","author":"Li Y","year":"2016","unstructured":"Li Y, Li J, Hou Z, Yu Y, Yu B. KLF5 overexpression attenuates cardiomyocyte inflammation induced by oxygen-glucose deprivation\/reperfusion through the PPAR\u03b3\/PGC-1\u03b1\/TNF-\u03b1 signaling pathway. Biomed Pharmacother. 2016;84:940\u2013946.","journal-title":"Biomed Pharmacother"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14910"},{"issue":"6","key":"e_1_3_3_30_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003572","article-title":"A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue","volume":"9","author":"Tina R","year":"2013","unstructured":"Tina R, Petr V, Cajsa D, Tasnim D, Elin H, Anders HO, Emma N, Asa T, Marloes DN, Karl-Fredrik E, et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLOS Genet. 2013;9(6): Article e1003572.","journal-title":"PLOS Genet"},{"issue":"4","key":"e_1_3_3_31_2","first-page":"408","article-title":"The influence of mechanical stimulation on osteocyte apoptosis and bone viability in human trabecular bone","volume":"6","author":"Mann VHC","year":"2006","unstructured":"Mann VHC, Kogianni G, Jones D, Noble B. The influence of mechanical stimulation on osteocyte apoptosis and bone viability in human trabecular bone. J Musculoskelet Neuronal Interact. 2006;6(4):408\u2013417.","journal-title":"J Musculoskelet Neuronal Interact"},{"issue":"4","key":"e_1_3_3_32_2","first-page":"369","article-title":"Methylation of bone SOST impairs SP7, RUNX2, and ER\u03b1 transactivation in patients with postmenopausal osteoporosis","volume":"97","author":"Yu Shan LW","year":"2018","unstructured":"Yu Shan LW, Li G, Shen G, Zhang P, Youjia X. Methylation of bone SOST impairs SP7, RUNX2, and ER\u03b1 transactivation in patients with postmenopausal osteoporosis. Biochem Cell Biol. 2018;97(4):369\u2013374.","journal-title":"Biochem Cell Biol"},{"key":"e_1_3_3_33_2","doi-asserted-by":"crossref","first-page":"771870","DOI":"10.3389\/fonc.2022.771870","article-title":"Epigenetic regulation of Ferroptosis-associated genes and its implication in cancer therapy","volume":"12","author":"Pei Y","year":"2022","unstructured":"Pei Y, Qian Y, Wang H, Tan L. Epigenetic regulation of Ferroptosis-associated genes and its implication in cancer therapy. Front Oncol. 2022;12:771870.","journal-title":"Front Oncol"},{"issue":"2","key":"e_1_3_3_34_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1021\/acschemneuro.1c00516","article-title":"PPAR-\u03b1 agonist GW7647 protects against oxidative stress and iron deposit via GPx4 in a transgenic mouse model of Alzheimer\u2019s diseases","volume":"13","author":"Qu XX","year":"2022","unstructured":"Qu XX, He JH, Cui ZQ, Yang T, Sun XH. PPAR-\u03b1 agonist GW7647 protects against oxidative stress and iron deposit via GPx4 in a transgenic mouse model of Alzheimer\u2019s diseases. ACS Chem Neurosci. 2022;13(2):207\u2013216.","journal-title":"ACS Chem Neurosci"},{"key":"e_1_3_3_35_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2023.102939","article-title":"HDAC3 aberration-incurred GPX4 suppression drives renal ferroptosis and AKI-CKD progression","volume":"68","author":"Zhang L","year":"2023","unstructured":"Zhang L, Chen F, Dong J, Wang R, Bi G, Xu D, Zhang Y, Deng Y, Lin W, Yang Z, et al. HDAC3 aberration-incurred GPX4 suppression drives renal ferroptosis and AKI-CKD progression. Redox Biol. 2023;68: Article 102939.","journal-title":"Redox Biol"},{"issue":"2","key":"e_1_3_3_36_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.gene.2013.09.080","article-title":"Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders","volume":"532","author":"Garc\u00eda-Ibarbia C","year":"2013","unstructured":"Garc\u00eda-Ibarbia C, Delgado-Calle J, Casafont I, Velasco J, Arozamena J, P\u00e9rez-N\u00fa\u00f1ez MI, Alonso MA, Berciano MT, Ortiz F, P\u00e9rez-Castrill\u00f3n JL, et al. Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders. Gene. 2013;532(2):165\u2013172.","journal-title":"Gene"},{"issue":"11","key":"e_1_3_3_37_2","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.4161\/cbt.4.11.2090","article-title":"KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells","volume":"4","author":"Yang Y","year":"2014","unstructured":"Yang Y, Goldstein BG, Chao H-H, Katz J. KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells. Cancer Biol Ther. 2014;4(11):1216\u20131221.","journal-title":"Cancer Biol Ther"},{"issue":"1","key":"e_1_3_3_38_2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41413-022-00198-w","article-title":"Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis","volume":"10","author":"Yang Y","year":"2022","unstructured":"Yang Y, Lin Y, Wang M, Yuan K, Wang Q, Mu P, du J, Yu Z, Yang S, Huang K, et al. Targeting ferroptosis suppresses osteocyte glucolipotoxicity and alleviates diabetic osteoporosis. Bone Res. 2022;10(1):26.","journal-title":"Bone Res"},{"issue":"1","key":"e_1_3_3_39_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41420-022-00902-z","article-title":"The NSUN5-FTH1\/FTL pathway mediates ferroptosis in bone marrow-derived mesenchymal stem cells","volume":"8","author":"Jie L","year":"2022","unstructured":"Jie L, Zhenxing R, Lin Y, Lulu Z, Yi L, Caiqun B, Helu L, Yichun J, Dongfeng C, Meiling Z, et al. The NSUN5-FTH1\/FTL pathway mediates ferroptosis in bone marrow-derived mesenchymal stem cells. Cell Death Discov. 2022;8(1):99.","journal-title":"Cell Death Discov"},{"issue":"1","key":"e_1_3_3_40_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s12011-021-02627-z","article-title":"Mitochondrial ferritin deficiency promotes osteoblastic ferroptosis via mitophagy in type 2 diabetic osteoporosis","volume":"200","author":"Wang X","year":"2021","unstructured":"Wang X, Ma H, Sun J, Zheng T, Zhao P, Li H, Yang MW. Mitochondrial ferritin deficiency promotes osteoblastic ferroptosis via mitophagy in type 2 diabetic osteoporosis. Biol Trace Elem Res. 2021;200(1):298\u2013307.","journal-title":"Biol Trace Elem Res"},{"key":"e_1_3_3_41_2","doi-asserted-by":"crossref","first-page":"1189513","DOI":"10.3389\/fendo.2023.1189513","article-title":"Identification of ferroptosis-related molecular clusters and genes for diabetic osteoporosis based on the machine learning","volume":"14","author":"Wang X","year":"2023","unstructured":"Wang X, Meng L, Zhang J, Zhao Z, Zou L, Jia Z, Han X, Zhao L, Song M, Zong J, et al. Identification of ferroptosis-related molecular clusters and genes for diabetic osteoporosis based on the machine learning. Front Endocrinol. 2023;14:1189513.","journal-title":"Front Endocrinol"},{"key":"e_1_3_3_42_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.freeradbiomed.2013.08.005","article-title":"Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differentiation","volume":"65","author":"Hyeon S","year":"2013","unstructured":"Hyeon S, Lee H, Yang Y, Jeong W. Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast differentiation. Free Radic Biol Med. 2013;65:789\u2013799.","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"e_1_3_3_43_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbrc.2003.12.073","article-title":"Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-\u03baB","volume":"314","author":"Bai X-c","year":"2004","unstructured":"Bai X-c, Lu D, Bai J, Zheng H, Ke Z-y, Li X-m, Luo SQ. Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-\u03baB. Biochem Biophys Res Commun. 2004;314(1):197\u2013207.","journal-title":"Biochem Biophys Res Commun"},{"issue":"9","key":"e_1_3_3_44_2","doi-asserted-by":"crossref","first-page":"8046","DOI":"10.1016\/j.actbio.2013.05.005","article-title":"Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms","volume":"9","author":"Gallo J","year":"2013","unstructured":"Gallo J, Goodman SB, Konttinen YT, Wimmer MA, Holinka M. Osteolysis around total knee arthroplasty: A review of pathogenetic mechanisms. Acta Biomater. 2013;9(9):8046\u20138058.","journal-title":"Acta Biomater"},{"issue":"4","key":"e_1_3_3_45_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.nefro.2020.03.005","article-title":"Ferroptosis and kidney disease","volume":"40","author":"Martin-Sanchez D","year":"2020","unstructured":"Martin-Sanchez D, Fontecha-Barriuso M, Martinez-Moreno JM, Ramos AM, Sanchez-Ni\u00f1o MD, Guerrero-Hue M, Moreno JA, Ortiz A, Sanz AB. Ferroptosis and kidney disease. Nefrologia. 2020;40(4):384\u2013394.","journal-title":"Nefrologia"},{"issue":"1","key":"e_1_3_3_46_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.beha.2014.11.002","article-title":"More is better: Combination therapies for myelodysplastic syndromes","volume":"28","author":"Moshe CO","year":"2015","unstructured":"Moshe CO, Sudipto M, Mikkael AS. More is better: Combination therapies for myelodysplastic syndromes. Best Pract Res Clin Haematol. 2015;28(1):22\u201331.","journal-title":"Best Pract Res Clin Haematol"},{"issue":"7","key":"e_1_3_3_47_2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"18","author":"Percie du Sert N","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLOS Biol. 2020;18(7): Article e3000410.","journal-title":"PLOS Biol"},{"issue":"1","key":"e_1_3_3_48_2","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13526","article-title":"Inhibition of DNA methyltransferase aberrations reinstates antioxidant aging suppressors and ameliorates renal aging","volume":"21","author":"Gao Q","year":"2021","unstructured":"Gao Q, Chen F, Zhang L, Wei A, Wang Y, Wu Z, Cao W. Inhibition of DNA methyltransferase aberrations reinstates antioxidant aging suppressors and ameliorates renal aging. Aging Cell. 2021;21(1): Article e13526.","journal-title":"Aging Cell"},{"key":"e_1_3_3_49_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s13075-015-0774-3","article-title":"Histone deacetylase inhibition activates Nrf2 and protects against osteoarthritis","volume":"17","author":"Cai D","year":"2015","unstructured":"Cai D, Yin S, Yang J, Jiang Q, Cao W. Histone deacetylase inhibition activates Nrf2 and protects against osteoarthritis. Arthritis Res Ther. 2015;17:269.","journal-title":"Arthritis Res Ther"},{"key":"e_1_3_3_50_2","first-page":"9","article-title":"Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis","volume":"2021","author":"Chen X","year":"2021","unstructured":"Chen X, Zhu X, Wei A, Chen F, Gao Q, Lu K, Jiang Q, Cao W. Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis. Bone Res. 2021;2021:9.","journal-title":"Bone Res"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.34133\/research.0021"},{"issue":"3","key":"e_1_3_3_52_2","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/S0014-5793(99)00696-1","article-title":"Ratio-fluorescence microscopy of lipid oxidation in living cells using C11-BODIPY581\/591","volume":"453","author":"Pap EHW","year":"1999","unstructured":"Pap EHW, Drummen GPC, Winter VJ, Kooij TWA, Rijken P, Wirtz KWA, op den Kamp JAF, Hage WJ, Post JA. Ratio-fluorescence microscopy of lipid oxidation in living cells using C11-BODIPY581\/591. FEBS Lett. 1999;453(3):278\u2013282.","journal-title":"FEBS Lett"},{"key":"e_1_3_3_53_2","first-page":"9839368","article-title":"Trans-2-enoyl-CoA reductase Tecr-driven lipid metabolism in endothelial cells protects against transcytosis to maintain blood-brain barrier homeostasis","volume":"2022","author":"Wang J","year":"2022","unstructured":"Wang J, Xu J, Zang G, Zhang T, Wu Q, Zhang H, Chen Y, Wang Y, Qin W, Zhao S, et al. Trans-2-enoyl-CoA reductase Tecr-driven lipid metabolism in endothelial cells protects against transcytosis to maintain blood-brain barrier homeostasis. Research. 2022;2022:9839368.","journal-title":"Research"},{"issue":"11","key":"e_1_3_3_54_2","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/bioinformatics\/18.11.1427","article-title":"MethPrimer designing primers for methylation PCRs","volume":"18","author":"Li L-C","year":"2002","unstructured":"Li L-C, Dahiya R. MethPrimer designing primers for methylation PCRs. Bioinformatics. 2002;18(11):1427\u20131431.","journal-title":"Bioinformatics"},{"issue":"10","key":"e_1_3_3_55_2","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1136\/annrheumdis-2018-214940","article-title":"PPAR\u03b3 preservation via promoter demethylation alleviates osteoarthritis in mice","volume":"78","author":"Zhu X","year":"2019","unstructured":"Zhu X, Chen F, Lu K, Wei A, Jiang Q, Cao W. PPAR\u03b3 preservation via promoter demethylation alleviates osteoarthritis in mice. Ann Rheum Dis. 2019;78(10):1420\u20131429.","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"e_1_3_3_56_2","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/s41418-020-00631-9","article-title":"Histone deacetylase 3 aberration inhibits klotho transcription and promotes renal fibrosis","volume":"28","author":"Chen F","year":"2020","unstructured":"Chen F, Gao Q, Wei A, Chen X, Shi Y, Wang H, Cao W. Histone deacetylase 3 aberration inhibits klotho transcription and promotes renal fibrosis. Cell Death Differ. 2020;28(3):1001\u20131012.","journal-title":"Cell Death Differ"},{"key":"e_1_3_3_57_2","volume-title":"Statistical power analysis for the behavioral sciences","author":"Cohen J","year":"1988","unstructured":"Cohen J. Statistical power analysis for the behavioral sciencesHillsdale (NJ): Erlbaum; 1988."}],"container-title":["Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/spj.science.org\/doi\/pdf\/10.34133\/research.0457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T07:03:09Z","timestamp":1724050989000},"score":1,"resource":{"primary":{"URL":"https:\/\/spj.science.org\/doi\/10.34133\/research.0457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":56,"alternative-id":["10.34133\/research.0457"],"URL":"https:\/\/doi.org\/10.34133\/research.0457","relation":{},"ISSN":["2639-5274"],"issn-type":[{"value":"2639-5274","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2024-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"0457"}}