{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:16:17Z","timestamp":1765545377667},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Differential expression of TBP-2 and Trx-1 occurs during osteoclastogenesis. Adenoviral overexpression of TBP-2 in osteoclast precursors inhibits Trx-1 expression, osteoclast formation, and AP-1 binding activity. TBP-2 and Trx-1 are key regulators of osteoclastogenesis.<\/jats:p>\n               <jats:p>Introduction: Thioredoxin binding protein-2 (TBP-2) negatively regulates thioredoxin-1 (Trx-1), a key endogenous modulator of cellular redox and signaling. In gene array analysis, we found that TBP-2 expression was reduced during human osteoclast differentiation compared with macrophage differentiation. Our aim was to determine the roles of TBP-2 and Trx-1 in human osteoclastogenesis and RANKL signaling.<\/jats:p>\n               <jats:p>Materials and Methods: Osteoclasts or macrophages were generated from colony-forming unit-granulocyte macrophage (CFU-GM) precursors treated with sRANKL and macrophage-colony-stimulating factor (M-CSF), or M-CSF alone, respectively. Expression of TBP-2 and Trx-1 was quantified by real-time PCR and Western analysis. Adenoviral gene transfer was used to overexpress TBP-2 in precursors. NF-\u03baB and activator protein 1 (AP-1) signaling was assessed with EMSA.<\/jats:p>\n               <jats:p>Results: In the presence of sRANKL, expression of TBP-2 was decreased, whereas Trx-1 expression was increased. The antioxidant N-acetylcysteine reversed this pattern and markedly inhibited osteoclastogenesis. Adenoviral overexpression of human TBP-2 in precursors inhibited osteoclastogenesis and Trx-1 expression, inhibited sRANKL-induced DNA binding of AP-1, but enhanced sRANKL-induced DNA binding of NF-\u03baB.<\/jats:p>\n               <jats:p>Conclusions: These data support significant roles for TBP-2 and the Trx system in osteoclast differentiation that are mediated by redox regulation of AP-1 transcription. A likely mechanism of stress signal induction of bone resorption is provided. Modulators of the Trx system such as antioxidants have potential as antiresorptive therapies.<\/jats:p>","DOI":"10.1359\/jbmr.040913","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T06:05:46Z","timestamp":1146117946000},"page":"2057-2064","source":"Crossref","is-referenced-by-count":37,"title":["Regulation of Human Osteoclast Differentiation by Thioredoxin Binding Protein-2 and Redox-Sensitive Signaling"],"prefix":"10.1093","volume":"19","author":[{"given":"Cathy J","family":"Aitken","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Victoria, Australia"}]},{"given":"Jason M","family":"Hodge","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Victoria, Australia"}]},{"given":"Yumiko","family":"Nishinaka","sequence":"additional","affiliation":[{"name":"Biomedical Special Research Unit, Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Osaka, Japan"}]},{"given":"Tanya","family":"Vaughan","sequence":"additional","affiliation":[{"name":"School of Health Science, Gold Coast Campus, Griffith University, Queensland, Australia"}]},{"given":"Junji","family":"Yodoi","sequence":"additional","affiliation":[{"name":"Biomedical Special Research Unit, Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Osaka, Japan"}]},{"given":"Christopher J","family":"Day","sequence":"additional","affiliation":[{"name":"School of Health Science, Gold Coast Campus, Griffith University, Queensland, Australia"}]},{"given":"Nigel A","family":"Morrison","sequence":"additional","affiliation":[{"name":"School of Health Science, Gold Coast Campus, Griffith University, Queensland, Australia"}]},{"given":"Geoffrey C","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Victoria, Australia"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019182820900_bib1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00018.2001","article-title":"Free radicals in the physiological control of cell function","volume":"82","author":"Droge","year":"2002","journal-title":"Physiol Rev"},{"key":"2024013019182820900_bib2","doi-asserted-by":"crossref","first-page":"13963","DOI":"10.1016\/S0021-9258(18)71625-6","article-title":"Thioredoxin and glutaredoxin systems","volume":"264","author":"Holmgren","year":"1989","journal-title":"J Biol Chem"},{"key":"2024013019182820900_bib3","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1089\/ars.2000.2.4-811","article-title":"Antioxidant function of thioredoxin and glutaredoxin systems","volume":"2","author":"Holmgren","year":"2000","journal-title":"Antioxid Redox Signal"},{"key":"2024013019182820900_bib4","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0898-6568(02)00053-0","article-title":"Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors","volume":"14","author":"Haddad","year":"2002","journal-title":"Cell Signal"},{"issue":"3","key":"2024013019182820900_bib5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"42","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"2024013019182820900_bib6","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s002239900512","article-title":"The relation of dietary vitamin C intake to bone mineral density: Results from the PEPI study","volume":"63","author":"Hall","year":"1998","journal-title":"Calcif Tissue Int"},{"key":"2024013019182820900_bib7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1359\/jbmr.1999.14.1.129","article-title":"Smoking, antioxidant vitamins, and the risk of hip fracture","volume":"14","author":"Melhus","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024013019182820900_bib8","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1136\/jech.51.5.479","article-title":"Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA","volume":"51","author":"Leveille","year":"1997","journal-title":"J Epidemiol Community Health"},{"key":"2024013019182820900_bib9","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/BF02652558","article-title":"Associations of vitamin C, calcium and protein with bone mass in postmenopausal Mexican American women","volume":"7","author":"Wang","year":"1997","journal-title":"Osteoporos Int"},{"key":"2024013019182820900_bib10","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1359\/jbmr.2001.16.1.135","article-title":"Vitamin C supplement use and bone mineral density in postmenopausal women","volume":"16","author":"Morton","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019182820900_bib11","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1007\/s00198-003-1391-6","article-title":"Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age","volume":"14","author":"Kaptoge","year":"2003","journal-title":"Osteoporos Int"},{"key":"2024013019182820900_bib12","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1210\/jc.2002-021496","article-title":"Marked decrease in plasma antioxidants in aged osteoporotic women: Results of a cross-sectional study","volume":"88","author":"Maggio","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019182820900_bib13","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/bbrc.2001.5747","article-title":"Association between oxidative stress and bone mineral density","volume":"288","author":"Basu","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019182820900_bib14","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S0006-291X(05)80311-0","article-title":"Stimulation of osteoclastic bone resorption by hydrogen peroxide","volume":"183","author":"Bax","year":"1992","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019182820900_bib15","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1172\/JCI114485","article-title":"Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo","volume":"85","author":"Garrett","year":"1990","journal-title":"J Clin Invest"},{"key":"2024013019182820900_bib16","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/8756-3282(96)00177-9","article-title":"Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae","volume":"19","author":"Fraser","year":"1996","journal-title":"Bone"},{"key":"2024013019182820900_bib17","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/0304-4165(93)90116-P","article-title":"Participation of oxidative stress in the process of osteoclast differentiation","volume":"1157","author":"Suda","year":"1993","journal-title":"Biochim Biophys Acta"},{"key":"2024013019182820900_bib18","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/(SICI)1097-4652(199809)176:3<574::AID-JCP14>3.0.CO;2-#","article-title":"Involvement of hydrogen peroxide in the differentiation of clonal HD-11EM cells into osteoclast-like cells","volume":"176","author":"Steinbeck","year":"1998","journal-title":"J Cell Physiol"},{"key":"2024013019182820900_bib19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1006\/bbrc.1995.1184","article-title":"The role of reactive oxygen intermediates in osteoclastic bone resorption","volume":"207","author":"Hall","year":"1995","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019182820900_bib20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/109662003322233459","article-title":"Lycopene I\u2014effect on osteoclasts: Lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral resorption mediated by reactive oxygen species in rat bone marrow cultures","volume":"6","author":"Rao","year":"2003","journal-title":"J Med Food"},{"key":"2024013019182820900_bib21","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0891-5849(01)00610-4","article-title":"Oxidative stress modulates osteoblastic differentiation of vascular and bone cells","volume":"31","author":"Mody","year":"2001","journal-title":"Free Radic Biol Med"},{"key":"2024013019182820900_bib22","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/jbmr.5650081013","article-title":"Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase","volume":"8","author":"Ramamurthy","year":"1993","journal-title":"J Bone Miner Res"},{"key":"2024013019182820900_bib23","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00223-001-1110-2","article-title":"Hydrogen peroxide induces apoptosis of osteocytes: Involvement of calcium ion and caspase activity","volume":"71","author":"Kikuyama","year":"2002","journal-title":"Calcif Tissue Int"},{"key":"2024013019182820900_bib24","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1172\/JCI200318859","article-title":"A crucial role for thiol antioxidants in estrogen-deficiency bone loss","volume":"112","author":"Lean","year":"2003","journal-title":"J Clin Invest"},{"key":"2024013019182820900_bib25","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1359\/JBMR.0301232","article-title":"Osteoclastic potential of human CFU-GM: Biphasic effect of GM-CSF","volume":"19","author":"Hodge","year":"2004","journal-title":"J Bone Miner Res"},{"key":"2024013019182820900_bib26","doi-asserted-by":"crossref","first-page":"21645","DOI":"10.1074\/jbc.274.31.21645","article-title":"Identification of thioredoxin-binding protein-2\/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression","volume":"274","author":"Nishiyama","year":"1999","journal-title":"J Biol Chem"},{"key":"2024013019182820900_bib27","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1006\/bbrc.2000.2699","article-title":"A possible interaction of thioredoxin with VDUP1 in HeLa cells detected in a yeast two-hybrid system","volume":"271","author":"Yamanaka","year":"2000","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013019182820900_bib28","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/15216540252774739","article-title":"Redox regulation by thioredoxin and thioredoxin-binding proteins","volume":"52","author":"Nishiyama","year":"2001","journal-title":"IUBMB Life"},{"key":"2024013019182820900_bib29","doi-asserted-by":"crossref","first-page":"6287","DOI":"10.4049\/jimmunol.164.12.6287","article-title":"Vitamin D3 up-regulated protein 1 mediates oxidative stress via suppressing the thioredoxin function","volume":"164","author":"Junn","year":"2000","journal-title":"J Immunol"},{"key":"2024013019182820900_bib30","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/dbio.1996.0208","article-title":"Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene","volume":"178","author":"Matsui","year":"1996","journal-title":"Dev Biol"},{"key":"2024013019182820900_bib31","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1158\/0008-5472.CAN-03-0908","article-title":"Loss of thioredoxin-binding protein-2\/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type 1-dependent T-cell transformation: Implications for adult T-cell leukemia leukemogenesis","volume":"64","author":"Nishinaka","year":"2004","journal-title":"Cancer Res"},{"key":"2024013019182820900_bib32","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1042\/cs0990133","article-title":"Induction of osteoclasts from CD14-positive human peripheral blood mononuclear cells by receptor activator of nuclear factor kappaB ligand (RANKL)","volume":"99","author":"Nicholson","year":"2000","journal-title":"Clin Sci (Lond)"},{"key":"2024013019182820900_bib33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3460001","article-title":"Thioredoxin reductase","volume":"346","author":"Mustacich","year":"2000","journal-title":"Biochem J"},{"key":"2024013019182820900_bib34","doi-asserted-by":"crossref","first-page":"8579","DOI":"10.1073\/pnas.122061399","article-title":"Ebselen: A substrate for human thioredoxin reductase strongly stimulating its hydroperoxide reductase activity and a superfast thioredoxin oxidant","volume":"99","author":"Zhao","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019182820900_bib35","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/0167-4781(94)90242-9","article-title":"Isolation and characterization of a novel cDNA from HL-60 cells treated with 1,25-dihydroxyvitamin D-3","volume":"1219","author":"Chen","year":"1994","journal-title":"Biochim Biophys Acta"},{"key":"2024013019182820900_bib36","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1210\/en.2002-220564","article-title":"Oligonucleotide microarray analysis of intact human pancreatic islets: Identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway","volume":"143","author":"Shalev","year":"2002","journal-title":"Endocrinology"},{"key":"2024013019182820900_bib37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/ng811","article-title":"Positional cloning of the combined hyperlipidemia gene Hyplip1","volume":"30","author":"Bodnar","year":"2002","journal-title":"Nat Genet"},{"key":"2024013019182820900_bib38","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1161\/01.RES.0000037982.55074.F6","article-title":"Vitamin D3-upregulated protein-1 (VDUP-1) regulates redox-dependent vascular smooth muscle cell proliferation through interaction with thioredoxin","volume":"91","author":"Schulze","year":"2002","journal-title":"Circ Res"},{"key":"2024013019182820900_bib39","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/(SICI)1098-2744(199604)15:4<251::AID-MC2>3.0.CO;2-J","article-title":"Alteration of gene expression in rat mammary tumors induced by N-methyl-N-nitrosourea","volume":"15","author":"Young","year":"1996","journal-title":"Mol Carcinog"},{"key":"2024013019182820900_bib40","first-page":"4045","article-title":"Vitamin D3 up-regulated protein 1 (VDUP1) expression in gastrointestinal cancer and its relation to stage of disease","volume":"22","author":"Ikarashi","year":"2002","journal-title":"Anticancer Res"},{"key":"2024013019182820900_bib41","first-page":"2425","article-title":"The thioredoxin-thioredoxin reductase system: Over-expression in human cancer","volume":"23","author":"Lincoln","year":"2003","journal-title":"Anticancer Res"},{"key":"2024013019182820900_bib42","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev.immunol.15.1.351","article-title":"Redox regulation of cellular activation","volume":"15","author":"Nakamura","year":"1997","journal-title":"Annu Rev Immunol"},{"key":"2024013019182820900_bib43","doi-asserted-by":"crossref","first-page":"27891","DOI":"10.1074\/jbc.274.39.27891","article-title":"Distinct roles of thioredoxin in the cytoplasm and in the nucleus. A two-step mechanism of redox regulation of transcription factor NF-kappaB","volume":"274","author":"Hirota","year":"1999","journal-title":"J Biol Chem"},{"key":"2024013019182820900_bib44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1179\/135100001101536427","article-title":"Regulatory roles of thioredoxin in oxidative stress-induced cellular responses","volume":"6","author":"Nishinaka","year":"2001","journal-title":"Redox Rep"},{"key":"2024013019182820900_bib45","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0014-5793(03)00430-7","article-title":"Oxidation of nuclear thioredoxin during oxidative stress","volume":"543","author":"Watson","year":"2003","journal-title":"FEBS Lett"},{"key":"2024013019182820900_bib46","doi-asserted-by":"crossref","first-page":"26496","DOI":"10.1074\/jbc.M202133200","article-title":"Vitamin D(3)-up-regulated protein-1 is a stress-responsive gene that regulates cardiomyocyte viability through interaction with thioredoxin","volume":"277","author":"Wang","year":"2002","journal-title":"J Biol Chem"},{"key":"2024013019182820900_bib47","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0378-4274(99)00024-7","article-title":"Intracellular oxidation\/reduction status in the regulation of transcription factors NF-kappaB and AP-1","volume":"106","author":"Gius","year":"1999","journal-title":"Toxicol Lett"},{"key":"2024013019182820900_bib48","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0891-5849(96)00501-1","article-title":"Redox regulation of NF-kappa B activation","volume":"22","author":"Flohe","year":"1997","journal-title":"Free Radic Biol Med"},{"key":"2024013019182820900_bib49","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/sj.cdd.4400959","article-title":"Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line","volume":"9","author":"Armstrong","year":"2002","journal-title":"Cell Death Differ"},{"key":"2024013019182820900_bib50","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1096\/fasebj.8.6.7909525","article-title":"Effect of glutathione depletion and oral N-acetyl-cysteine treatment on CD4+ and CD8+ cells","volume":"8","author":"Kinscherf","year":"1994","journal-title":"FASEB J"},{"key":"2024013019182820900_bib51","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1152\/physrev.1998.78.2.547","article-title":"The free radical theory of aging matures","volume":"78","author":"Beckman","year":"1998","journal-title":"Physiol Rev"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.040913","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/12\/2057\/56474339\/5650191217.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/12\/2057\/56474339\/5650191217.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:07:25Z","timestamp":1710342445000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/19\/12\/2057-2064\/7592752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,1]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2004,12,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.040913","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,12,1]]},"published":{"date-parts":[[2004,12,1]]}}}