{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T10:11:57Z","timestamp":1775211117764,"version":"3.50.1"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":110,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.jbc.2021.100696","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T17:57:49Z","timestamp":1619114269000},"page":"100696","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["The small molecule DIPQUO promotes osteogenic differentiation via inhibition of glycogen synthase kinase 3-beta signaling"],"prefix":"10.1016","volume":"296","author":[{"given":"Brandoch","family":"Cook","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qisheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-5187","authenticated-orcid":false,"given":"Shuibing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Evans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2021.100696_bib1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.jtemb.2014.08.010","article-title":"Osteoporosis in neurodegeneration","volume":"28","author":"Roos","year":"2014","journal-title":"J.\u00a0Trace Elem. Med. Biol."},{"key":"10.1016\/j.jbc.2021.100696_bib2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fphar.2014.00120","article-title":"Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling","volume":"5","author":"Cornelius","year":"2014","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jbc.2021.100696_bib3","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/s41419-018-1123-7","article-title":"APP promotes osteoblast survival and bone formation by regulating mitochondrial function and preventing oxidative stress","volume":"9","author":"Pan","year":"2018","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.jbc.2021.100696_bib4","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1093\/ageing\/afw137","article-title":"Association between osteocalcin and cognitive performance in healthy older adults","volume":"45","author":"Bradburn","year":"2016","journal-title":"Age Ageing"},{"key":"10.1016\/j.jbc.2021.100696_bib5","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.chembiol.2019.03.009","article-title":"Discovery of a small molecule promoting mouse and human osteoblast differentiation via activation of p38 MAPK-beta","volume":"26","author":"Cook","year":"2019","journal-title":"Cell Chem Biol."},{"key":"10.1016\/j.jbc.2021.100696_bib6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fcell.2016.00040","article-title":"p38 MAPK signaling in osteoblast differentiation","volume":"4","author":"Rodriguez-Carballo","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.jbc.2021.100696_bib7","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1172\/JCI42285","article-title":"The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice","volume":"120","author":"Greenblatt","year":"2010","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.jbc.2021.100696_bib8","doi-asserted-by":"crossref","first-page":"272","DOI":"10.7150\/ijbs.2929","article-title":"TGF-beta and BMP signaling in osteoblast differentiation and bone formation","volume":"8","author":"Chen","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.jbc.2021.100696_bib9","doi-asserted-by":"crossref","first-page":"16009","DOI":"10.1038\/boneres.2016.9","article-title":"TGF-beta and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease","volume":"4","author":"Wu","year":"2016","journal-title":"Bone Res."},{"key":"10.1016\/j.jbc.2021.100696_bib10","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/bonekey.2015.80","article-title":"Focus on the p38 MAPK signaling pathway in bone development and maintenance","volume":"4","author":"Thouverey","year":"2015","journal-title":"Bonekey Rep."},{"key":"10.1016\/j.jbc.2021.100696_bib11","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1083\/jcb.200610046","article-title":"Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development","volume":"176","author":"Ge","year":"2007","journal-title":"J.\u00a0Cell Biol."},{"key":"10.1016\/j.jbc.2021.100696_bib12","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1242\/dev.00491","article-title":"Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth","volume":"130","author":"Yu","year":"2003","journal-title":"Development"},{"key":"10.1016\/j.jbc.2021.100696_bib13","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1210\/en.2005-1502","article-title":"Regulation of osteoblast differentiation: A novel function for fibroblast growth factor 8","volume":"147","author":"Valta","year":"2006","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2021.100696_bib14","doi-asserted-by":"crossref","first-page":"40575","DOI":"10.1074\/jbc.M111.274910","article-title":"Fibroblast growth factor 2 stimulation of osteoblast differentiation and bone formation is mediated by modulation of the Wnt signaling pathway","volume":"286","author":"Fei","year":"2011","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100696_bib15","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1101\/gad.1089403","article-title":"Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2","volume":"17","author":"Peng","year":"2003","journal-title":"Genes Dev."},{"key":"10.1016\/j.jbc.2021.100696_bib16","doi-asserted-by":"crossref","first-page":"e1058","DOI":"10.1371\/journal.pone.0001058","article-title":"Akt1 in osteoblasts and osteoclasts controls bone remodeling","volume":"2","author":"Kawamura","year":"2007","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2021.100696_bib17","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fcell.2018.00170","article-title":"Wnt pathway in bone repair and regeneration - what do we know so far","volume":"6","author":"Houschyar","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.jbc.2021.100696_bib18","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1233606","article-title":"Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay","volume":"341","author":"Martinez Molina","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.jbc.2021.100696_bib19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev-pharmtox-010715-103715","article-title":"The cellular thermal shift assay: A novel biophysical assay for in situ drug target engagement and mechanistic biomarker studies","volume":"56","author":"Martinez Molina","year":"2016","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.jbc.2021.100696_bib20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00403-009-0929-7","article-title":"Inhibition of glycogen synthase kinase-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1 in human primary dermal papilla cell culture and maintains mouse hair bulbs in organ culture","volume":"301","author":"Yamauchi","year":"2009","journal-title":"Arch. Dermatol. Res."},{"key":"10.1016\/j.jbc.2021.100696_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035892","article-title":"Pleiotropy of glycogen synthase kinase-3 inhibition by CHIR99021 promotes self-renewal of embryonic stem cells from refractory mouse strains","volume":"7","author":"Ye","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2021.100696_bib22","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.bone.2011.11.007","article-title":"GSK-3 inhibition by an orally active small molecule increases bone mass in rats","volume":"50","author":"Marsell","year":"2012","journal-title":"Bone"},{"key":"10.1016\/j.jbc.2021.100696_bib23","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1242\/dev.129.12.2987","article-title":"Generation of different fates from multipotent muscle stem cells","volume":"129","author":"Wada","year":"2002","journal-title":"Development"},{"key":"10.1016\/j.jbc.2021.100696_bib24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0056641","article-title":"Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells","volume":"8","author":"Oishi","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2021.100696_bib25","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/beta-Catenin signaling, disease, and emerging therapeutic modalities","volume":"169","author":"Nusse","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.jbc.2021.100696_bib26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.biocel.2016.05.015","article-title":"The role of the wnt\/beta-catenin signaling pathway in formation and maintenance of bone and teeth","volume":"77","author":"Duan","year":"2016","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"10.1016\/j.jbc.2021.100696_bib27","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0960-9822(00)00246-3","article-title":"Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells","volume":"4","author":"Lovestone","year":"1994","journal-title":"Curr. Biol."},{"issue":"Pt 6","key":"10.1016\/j.jbc.2021.100696_bib28","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1242\/jcs.109.6.1537","article-title":"Cellular phosphorylation of tau by GSK-3 beta influences tau binding to microtubules and microtubule organisation","volume":"109","author":"Wagner","year":"1996","journal-title":"J.\u00a0Cell Sci."},{"key":"10.1016\/j.jbc.2021.100696_bib29","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1111\/j.1471-4159.2007.05194.x","article-title":"The GSK3 hypothesis of Alzheimer's disease","volume":"104","author":"Hooper","year":"2008","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.jbc.2021.100696_bib30","doi-asserted-by":"crossref","first-page":"24","DOI":"10.3389\/fnmol.2011.00024","article-title":"Modulation of GSK-3 as a therapeutic strategy on tau pathologies","volume":"4","author":"Medina","year":"2011","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.jbc.2021.100696_bib31","doi-asserted-by":"crossref","first-page":"24977","DOI":"10.1074\/jbc.M000808200","article-title":"Tau phosphorylation at serine 396 and serine 404 by human recombinant tau protein kinase II inhibits tau's ability to promote microtubule assembly","volume":"275","author":"Evans","year":"2000","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.jbc.2021.100696_bib32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fnmol.2014.00065","article-title":"Physiological and pathological phosphorylation of tau by Cdk5","volume":"7","author":"Kimura","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.jbc.2021.100696_bib33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.febslet.2005.11.059","article-title":"P70 S6 kinase mediates tau phosphorylation and synthesis","volume":"580","author":"Pei","year":"2006","journal-title":"FEBS Lett."},{"key":"10.1016\/j.jbc.2021.100696_bib34","doi-asserted-by":"crossref","first-page":"9626","DOI":"10.1021\/acs.jafc.7b03252","article-title":"Resveratrol ameliorates tau hyperphosphorylation at Ser396 site and oxidative damage in rat hippocampal slices exposed to vanadate: Implication of ERK1\/2 and GSK-3beta signaling cascades","volume":"65","author":"Jhang","year":"2017","journal-title":"J.\u00a0Agric. Food Chem."},{"key":"10.1016\/j.jbc.2021.100696_bib35","article-title":"A\u00a0mathematical model of multisite phosphorylation of tau protein","volume":"13","author":"Stepanov","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.jbc.2021.100696_bib36","doi-asserted-by":"crossref","first-page":"13635","DOI":"10.1523\/JNEUROSCI.3949-07.2007","article-title":"Insulin dysfunction induces in\u00a0vivo tau hyperphosphorylation through distinct mechanisms","volume":"27","author":"Planel","year":"2007","journal-title":"J.\u00a0Neurosci."},{"key":"10.1016\/j.jbc.2021.100696_bib37","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.pbb.2012.03.002","article-title":"Metformin attenuates Alzheimer's disease-like neuropathology in obese, leptin-resistant mice","volume":"101","author":"Li","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.jbc.2021.100696_bib38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fnins.2018.00044","article-title":"Phospho-tau bar code: Analysis of phosphoisotypes of tau and its application to tauopathy","volume":"12","author":"Kimura","year":"2018","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.jbc.2021.100696_bib39","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1210\/en.2013-1155","article-title":"GSK-3beta function in bone regulates skeletal development, whole-body metabolism, and male life span","volume":"154","author":"Gillespie","year":"2013","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2021.100696_bib40","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.bone.2008.10.001","article-title":"Lithium's effect on bone mineral density","volume":"44","author":"Zamani","year":"2009","journal-title":"Bone"},{"key":"10.1016\/j.jbc.2021.100696_bib41","doi-asserted-by":"crossref","first-page":"45204","DOI":"10.1038\/srep45204","article-title":"Acceleration of bone regeneration by activating Wnt\/beta-catenin signalling pathway via lithium released from lithium chloride\/calcium phosphate cement in osteoporosis","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jbc.2021.100696_bib42","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bone.2013.01.019","article-title":"Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation","volume":"54","author":"Sisask","year":"2013","journal-title":"Bone"},{"key":"10.1016\/j.jbc.2021.100696_bib43","doi-asserted-by":"crossref","first-page":"S547","DOI":"10.3233\/JAD-179934","article-title":"The conundrum of GSK3 inhibitors: Is it the dawn of a new beginning?","volume":"64","author":"Bhat","year":"2018","journal-title":"J.\u00a0Alzheimers Dis."},{"key":"10.1016\/j.jbc.2021.100696_bib44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fnmol.2012.00014","article-title":"Inhibition of GSK3 by lithium, from single molecules to signaling networks","volume":"5","author":"Freland","year":"2012","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.jbc.2021.100696_bib45","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.pharmthera.2014.11.016","article-title":"Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases","volume":"148","author":"Beurel","year":"2015","journal-title":"Pharmacol. Ther."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925821004853?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925821004853?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:07:11Z","timestamp":1758240431000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925821004853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":45,"alternative-id":["S0021925821004853"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2021.100696","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The small molecule DIPQUO promotes osteogenic differentiation via inhibition of glycogen synthase kinase 3-beta signaling","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2021.100696","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"100696"}}