{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:47:27Z","timestamp":1768812447986,"version":"3.49.0"},"reference-count":67,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["Grant agreement ID: 778277"],"award-info":[{"award-number":["Grant agreement ID: 778277"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0\u2013700 \u03bcM). Colostrum co-treated with DEX was executed at 0.1\u20135.0 mg\/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1\/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1\/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.<\/jats:p>","DOI":"10.3390\/ijms221910195","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T22:24:13Z","timestamp":1632695053000},"page":"10195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1612-2726","authenticated-orcid":false,"given":"Sagrario","family":"Martin-Aragon","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Complutense University, 28040 Madrid, Spain"}]},{"given":"Paloma","family":"Bermejo-Besc\u00f3s","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Complutense University, 28040 Madrid, Spain"}]},{"given":"Juana","family":"Bened\u00ed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Complutense University, 28040 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4817-761X","authenticated-orcid":false,"given":"Carlos","family":"Raposo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacognosy and Botany, Complutense University, 28040 Madrid, Spain"},{"name":"SALURIS, 28040 Madrid, Spain"}]},{"given":"Franklim","family":"Marques","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7320-212X","authenticated-orcid":false,"given":"Eirini K.","family":"Kydonaki","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal"}]},{"given":"Paraskevi","family":"Gkiata","sequence":"additional","affiliation":[{"name":"School of Sport and Exercise Sciences, University of Thessaly, Karies, 42100 Trikala, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-9447","authenticated-orcid":false,"given":"Yiannis","family":"Koutedakis","sequence":"additional","affiliation":[{"name":"School of Sport and Exercise Sciences, University of Thessaly, Karies, 42100 Trikala, Greece"},{"name":"Faculty of Education, Health and Wellbeing, Wolverhampton University, Walsall WV1 1LY, UK"}]},{"given":"Georgia","family":"Ntina","sequence":"additional","affiliation":[{"name":"BME, Biomechanical Solutions, 43150 Karditsa, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2293-079X","authenticated-orcid":false,"given":"Andres E.","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Department of Exercise Science, Chatham University, Pittsburgh, PA 15232, USA"},{"name":"Move-Cor Inc., Pittsburgh, PA 15017, USA"}]},{"given":"T\u00e2nia","family":"Amorim","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s40279-013-0100-7","article-title":"Bone quality: The determinants of bone strength and fragility","volume":"44","author":"Fonseca","year":"2014","journal-title":"Sports Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S0140-6736(17)32640-5","article-title":"Screening in the community to reduce fractures in older women (SCOOP): A randomised controlled trial","volume":"391","author":"Shepstone","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s40279-014-0268-5","article-title":"Prevalence of Low Bone Mineral Density in Female Dancers","volume":"45","author":"Amorim","year":"2015","journal-title":"Sports Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1007\/s00198-017-4130-0","article-title":"Bone mineral density in vocational and professional ballet dancers","volume":"28","author":"Amorim","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11914-016-0320-5","article-title":"Risk Factors, Epidemiology and Treatment Strategies for Metabolic Bone Disease in Patients with Neurological Disease","volume":"14","author":"Binks","year":"2016","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/bs.irn.2019.06.002","article-title":"Potential exerkines for physical exercise-elicited pro-cognitive effects: Insight from clinical and animal research","volume":"147","author":"Lee","year":"2019","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1001\/archneur.62.1.107","article-title":"Bone Mineral Density and the Risk of Alzheimer Disease","volume":"62","author":"Tan","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4103\/tcmj.tcmj_54_17","article-title":"Alzheimer\u2019s disease and osteoporosis","volume":"29","author":"Chena","year":"2017","journal-title":"Tzu-Chi Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.tem.2013.12.006","article-title":"Glucocorticoids and bone: Local effects and systemic implications","volume":"25","author":"Henneicke","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s12020-018-1588-2","article-title":"Glucocorticoid-induced osteoporosis: An update","volume":"61","author":"Compston","year":"2018","journal-title":"Endocrine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1007\/s11064-019-02779-4","article-title":"Mitochondrial Dynamics Impairment in Dexamethasone-Treated Neuronal Cells","volume":"44","author":"Suwanjang","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_12","first-page":"1606","article-title":"Prevention of osteoporosis by foods and dietary supplements. Prevention of osteoporosis by milk and dairy products","volume":"16","author":"Uenishi","year":"2006","journal-title":"Clin. Calcium."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jri.2015.06.001","article-title":"Immunoglobulin G concentration in canine colostrum: Evaluation and variability","volume":"112","author":"Mila","year":"2015","journal-title":"J. Reprod. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7608","DOI":"10.3168\/jds.2019-16421","article-title":"Graduate Student Literature Review: The milk behind the mustache: A review of milk and bone biology","volume":"102","author":"Batty","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"563","DOI":"10.17219\/acem\/62536","article-title":"An animal model of the procognitive properties of cysteine protease inhibitor and immunomodulatory peptides based on colostrum","volume":"26","author":"Polanowski","year":"2017","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/j.1439-0531.2006.00799.x","article-title":"Antioxidants in Bovine Colostrum","volume":"42","author":"Przybylska","year":"2007","journal-title":"Reprod. Domest. Anim."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1017\/S0022029920000813","article-title":"Colostrum from primiparous Holstein cows shows higher antioxidant activity than colostrum of multiparous ones","volume":"87","author":"Moretti","year":"2020","journal-title":"J. Dairy Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e547","DOI":"10.11607\/jomi.te35","article-title":"Effect of proline-rich synthetic peptide-coated titanium implants on bone healing in a rabbit model","volume":"28","author":"Petzold","year":"2013","journal-title":"Int. J. Oral. Maxillofac. Implants."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.pnpbp.2018.05.013","article-title":"The role of monoamines in the development of Alzheimer\u2019s disease and neuroprotective effect of a proline rich polypeptide","volume":"86","author":"Yenkoyan","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S59","DOI":"10.1017\/S0007114500002269","article-title":"Nucleosides and nucleotides: Natural bioactive substances in milk and colostrum","volume":"84","author":"Schlimme","year":"2000","journal-title":"Br. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1007\/s12603-009-0102-1","article-title":"The protective effects of the nutraceutical, colostrinin, against Alzheimer\u2019s disease, is mediated via prevention of apoptosis in human neurones induced by aggregated beta-amyloid","volume":"13","author":"Matharu","year":"2009","journal-title":"J. Nutr. Health Aging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.3892\/ijmm.2012.1087","article-title":"Insulin-like growth factor-1 protects against prion peptide-induced cell death in neuronal cells via inhibition of Bax translocation","volume":"30","author":"Park","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/biof.5520290403","article-title":"Involvement of ligand occupancy in Insulin-like growth factor-I (IGF-I) induced cell growth in osteoblast like MC3T3-E1 cells","volume":"29","author":"Kim","year":"2007","journal-title":"Biofactors"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"01100","DOI":"10.3389\/fphar.2020.01100","article-title":"Therapeutic Applications of Human and Bovine Colostrum in the Treatment of Gastrointestinal Diseases and Distinctive Cancer Types: The Current Evidence","volume":"11","author":"Yadav","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.3168\/jds.S0022-0302(91)78627-X","article-title":"Insulin in bovine colostrum and milk: Evolution throughout lactation and binding to caseins","volume":"74","author":"Aranda","year":"1991","journal-title":"J. Dairy Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1055\/s-2006-925119","article-title":"Leptin in bovine colostrum and milk","volume":"38","author":"Pinotti","year":"2006","journal-title":"Horm. Metab. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s11745-013-3803-5","article-title":"Synergism of \u03b1-Linolenic Acid, Conjugated Linoleic Acid and Calcium in Decreasing Adipocyte and Increasing Osteoblast Cell Growth","volume":"48","author":"Kim","year":"2013","journal-title":"Lipids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ijbiomac.2017.08.151","article-title":"Lactoferrin promotes MC3T3-E1 osteoblast cells proliferation via MAPK signaling pathways","volume":"107","author":"Liu","year":"2018","journal-title":"Int. J. Biol Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s00198-007-0394-0","article-title":"Glucocorticoid-induced osteoporosis: Pathophysiology and therapy","volume":"18","author":"Canalis","year":"2007","journal-title":"Osteoporos. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cbi.2013.11.004","article-title":"Effect of glucocorticoid-induced oxidative stress on the expression of Cbfa1","volume":"207","author":"Feng","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.11138\/ccmbm\/2017.14.1.209","article-title":"Oxidative stress in bone remodeling: Role of antioxidants","volume":"14","author":"Domazetovic","year":"2017","journal-title":"Clin. Cases Miner Bone Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/jbmr.5650050803","article-title":"Long-term effects of physiologic concentrations of dexamethasone on human bone-derived cells","volume":"5","author":"Wong","year":"1990","journal-title":"J. Bone Miner. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1559325819889819","DOI":"10.1177\/1559325819889819","article-title":"Biphasic Dose Response and Hormetic Effects of Stress Hormone Hydrocortisone on Telomerase-Immortalized Human Bone Marrow Stem Cells In Vitro","volume":"17","author":"Gopi","year":"2019","journal-title":"Dose Response."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1080\/09168451.2014.896733","article-title":"Presence of osteoinductive factors in bovine colostrum","volume":"78","author":"Mussano","year":"2014","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10495-020-01599-0","article-title":"Glucocorticoid-induced autophagy and apoptosis in bone","volume":"25","author":"Wang","year":"2020","journal-title":"Apoptosis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1006\/abio.2000.4498","article-title":"Determining glutathione and glutathione disulfide using the fluorescence probe o-phthalaldehyde","volume":"280","author":"Senft","year":"2000","journal-title":"Anal. Biochem."},{"key":"ref_37","first-page":"322","article-title":"Inhibition of PI3-kinase-Akt pathway enhances dexamethasone-induced apoptosis in a human follicular lymphoma cell line","volume":"312","author":"Nuutinen","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.neuint.2013.07.007","article-title":"Antidepressants attenuate the dexamethasone induced decrease in viability and proliferation of human neuroblastoma SH-SY5Y cells: A involvement of extracellular regulated kinase (ERK1\/2)","volume":"63","author":"Leskiewicz","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1042\/BST20120080","article-title":"Insulin and IGF-1 signalling: Longevity, protein homoeostasis and Alzheimer\u2019s disease","volume":"40","author":"Kiely","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1385\/JMN:17:3:379","article-title":"Towards an understanding of biological role of Colostrinin peptides","volume":"17","author":"Kruzel","year":"2001","journal-title":"Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3233\/JAD-2008-13308","article-title":"ColostrininTM: An Oxidative Stress Modulator for Prevention and Treatment of Age-related Disorders","volume":"13","author":"Boldogh","year":"2008","journal-title":"J. Alzheimers Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.neuint.2016.05.003","article-title":"Melatonin prevents cytosolic calcium overload, mitochondrial damage and cell death due to toxically high doses of dexamethasone-induced oxidative stress in human neuroblastoma SH-SY5Y cells","volume":"97","author":"Suwanjang","year":"2016","journal-title":"Neurochem. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1530\/JME-19-0003","article-title":"Lactoferrin ameliorates aging-suppressed osteogenesis via IGF1 signaling","volume":"63","author":"Chen","year":"2019","journal-title":"J. Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2174\/1389203716666150102110817","article-title":"Proline-rich peptides: Multifunctional bioactive molecules as new potential therapeutic drugs","volume":"16","author":"Vitali","year":"2015","journal-title":"Curr. Protein. Pept. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1073\/pnas.95.2.554","article-title":"Modulation of cell death by Bcl-XL through caspase interaction","volume":"95","author":"Clem","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1615\/CritRevEukaryotGeneExpr.v13.i24.140","article-title":"Role of apoptosis in glucocorticoid-induced osteoporosis and osteonecrosis","volume":"13","author":"Zalavras","year":"2003","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11010-011-1105-x","article-title":"Cell apoptosis induced by zinc deficiency in osteoblastic MC3T3-E1 cells via a mitochondrial-mediated pathway","volume":"361","author":"Guo","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/CJP.CJP_7_19","article-title":"Different susceptibilities of osteoclasts and osteoblasts to glucocorticoid-induced oxidative stress and mitochondrial alterations","volume":"62","author":"Chen","year":"2019","journal-title":"Chin. J. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1074\/jbc.M805432200","article-title":"Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1\/2 and protein kinase C signaling","volume":"284","author":"Miraoui","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1359\/JBMR.0301242","article-title":"Prevention of glucocorticoid-induced apoptosis in osteocytes and osteoblasts by calbindin-D28k","volume":"19","author":"Liu","year":"2004","journal-title":"J. Bone Miner Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/BF02555005","article-title":"Insulin-like growth factor-I and insulin-like growth factor-II induce c-fos in mouse osteoblastic cells","volume":"46","author":"Merriman","year":"1990","journal-title":"Calcif. Tissue Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.3892\/mmr.2014.2374","article-title":"Platelet-derived growth factor promotes osteoblast proliferation by activating G-protein-coupled receptor kinase interactor-1","volume":"10","author":"Wu","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/1097-4644(20010501)81:2<304::AID-JCB1045>3.0.CO;2-U","article-title":"The cell survival signal Akt is differentially activated by PDGF-BB, EGF, and FGF-2 in osteoblastic cells","volume":"81","author":"Chaudhary","year":"2001","journal-title":"J. Cell Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"589","DOI":"10.4062\/biomolther.2016.030","article-title":"Insulin as a Potent Stimulator of Akt, ERK and Inhibin-\u03b2E signaling in Osteoblast-Like UMR-106 Cells","volume":"24","author":"Ramalingam","year":"2016","journal-title":"Biomol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/jcb.10221","article-title":"Specific induction of heat shock protein 27 by glucocorticoid in osteoblasts","volume":"86","author":"Kozawa","year":"2002","journal-title":"J. Cell Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s12038-007-0059-3","article-title":"Heat shock genes\u2014integrating cell survival and death","volume":"32","author":"Arya","year":"2007","journal-title":"J. Biosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1021\/acs.jmedchem.8b00825","article-title":"Allosteric Modulators of HSP90 and HSP70: Dynamics Meets Function through Structure-Based Drug Design","volume":"62","author":"Ferraro","year":"2019","journal-title":"Rev. J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"G477","DOI":"10.1152\/ajpgi.00281.2010","article-title":"The nutraceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes","volume":"300","author":"Marchbank","year":"2011","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.bbrc.2015.11.125","article-title":"Heat shock protein 70-1A is a novel angiogenic regulator","volume":"469","author":"Kim","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"100370","DOI":"10.1016\/j.jbo.2021.100370","article-title":"Differential expression of angiogenesis markers HSP70, HSP90, VEGF and pERK1\/2 in both components of dedifferentiated chondrosarcomas","volume":"29","author":"Schoedel","year":"2021","journal-title":"J. Bone Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.biopha.2018.11.103","article-title":"Dexamethasone induces osteoblast apoptosis through ROS-PI3K\/AKT\/GSK3\u03b2 signaling pathway","volume":"110","author":"Deng","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00204-017-2070-2","article-title":"P21(Waf1\/Cip1) depletion promotes dexamethasone-induced apoptosis in osteoblastic MC3T3-E1 cells by inhibiting the Nrf2\/HO-1 pathway","volume":"92","author":"Han","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_63","first-page":"1593","article-title":"Signaling pathways governing osteoblast proliferation, differentiation and function","volume":"24","author":"Chau","year":"2009","journal-title":"Histol. Histopathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3109\/08977199409019601","article-title":"Basic FGF and IGF-I promote differentiation of human SH-SY5Y neuroblastoma cells in culture","volume":"10","author":"Lavenius","year":"1994","journal-title":"Growth Factors."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"37371","DOI":"10.1038\/srep37371","article-title":"Glucocorticoid receptor and Histone deacetylase 6 mediate the differential effect of dexamethasone during osteogenesis of mesenchymal stromal cells (MSCs)","volume":"6","author":"Rimando","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1080\/21691401.2019.1609007","article-title":"The dosage effects of dexamethasone on osteogenic activity and biocompatibility of poly(lactic-co-glycolic acid)\/hydroxyapatite nanofibers","volume":"47","author":"Li","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10195\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:03:15Z","timestamp":1760166195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/19\/10195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,22]]},"references-count":67,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms221910195"],"URL":"https:\/\/doi.org\/10.3390\/ijms221910195","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,22]]}}}