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However, the molecular mechanisms behind DOX-induced bone loss have not been elucidated. Molecules that can protect against the adverse effects of DOX are still a challenge in chemotherapeutic treatments. We investigated the effect and mechanism of DOX in osteoclast differentiation and used the Sirt 1 activator resveratrol (RES) to counteract DOX-induced effects. RAW 264.7 cells were differentiated into osteoclasts under cotreatment with DOX and RES, alone or combined. RES treatment inhibited DOX-induced osteoclast differentiation, reduced the expression of osteoclast fusion marker Oc-stamp and osteoclast differentiation markers Rank, Trap, Ctsk and Nfatc1. Conversely, RES induced the upregulation of antioxidant genes Sod 1 and Nrf 2 while DOX significantly reduced the FoxM1 expression, resulting in oxidative stress. Treatment with the antioxidant MitoTEMPO did not influence DOX-induced osteoclast differentiation. DOX-induced osteoclastogenesis was studied using the cathepsin-K zebrafish reporter line (Tg[ctsk:DsRed]). DOX significantly increased ctsk signal, while RES cotreatment resulted in a significant reduction in ctsk positive cells. RES significantly rescued DOX-induced mucositis in this model. Additionally, DOX-exposed zebrafish displayed altered locomotor behavior and locomotory patterns, while RES significantly reversed these effects. Our research shows that RES prevents DOX-induced osteoclast fusion and activation in vitro and in vivo and reduces DOX-induced mucositis, while improving locomotion parameters.<\/jats:p>","DOI":"10.3390\/ijms232315160","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T03:55:37Z","timestamp":1669953337000},"page":"15160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Resveratrol-Mediated Reversal of Doxorubicin-Induced Osteoclast Differentiation"],"prefix":"10.3390","volume":"23","author":[{"given":"Sunil","family":"Poudel","sequence":"first","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal"},{"name":"PhD Program in Biomedical Sciences, FMCB, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1344-2954","authenticated-orcid":false,"given":"Gil","family":"Martins","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal"},{"name":"PhD Program in Biomedical Sciences, FMCB, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3114-6662","authenticated-orcid":false,"given":"M. Leonor","family":"Cancela","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center, University of Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-1957","authenticated-orcid":false,"given":"Paulo J.","family":"Gavaia","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences, University of Algarve, 8005-139 Faro, Portugal"},{"name":"Faculty of Medicine and Biomedical Sciences (FMCB), University of Algarve, 8005-139 Faro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1521020","DOI":"10.1155\/2017\/1521020","article-title":"Oxidative stress and cellular response to doxorubicin: A common factor in the complex milieu of anthracycline cardiotoxicity","volume":"2017","author":"Cappetta","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1016\/j.ejca.2009.09.026","article-title":"The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer","volume":"45","author":"Hadji","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1023\/A:1008352620870","article-title":"Effect of single chemotherapeutic agents on the growing skeleton of the rat","volume":"11","author":"Kamps","year":"2000","journal-title":"Ann. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"602","DOI":"10.2106\/00004623-198466040-00016","article-title":"Effects of chemotherapeutic agents on bone. I. Short-term methotrexate and doxorubicin (adriamycin) treatment in a rat model","volume":"66","author":"Friedlaender","year":"1984","journal-title":"J. Bone Jt. Surg. Ser. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00774-015-0656-4","article-title":"Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases","volume":"33","author":"Callaway","year":"2015","journal-title":"J. Bone Miner. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"L1005-28","DOI":"10.1152\/ajplung.2000.279.6.L1005","article-title":"Reactive oxygen species in cell signaling","volume":"279","author":"Thannickal","year":"2000","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.yexcr.2004.07.035","article-title":"Reactive oxygen species mediate rank signaling in osteoclasts","volume":"301","author":"Ha","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_8","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","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1182\/blood-2004-09-3662","article-title":"A Crucial Role for Reactive Oxygen Species in RANKL-Induced Osteoclast Differentiation","volume":"106","author":"Lee","year":"2005","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1124\/pr.110.002980","article-title":"NADPH oxidase-mediated redox signaling: Roles in cellular stress response, stress tolerance, and tissue repair","volume":"63","author":"Jiang","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13984","DOI":"10.1074\/jbc.M213067200","article-title":"The calcineurin\/nuclear factor of activated T cells signaling pathway regulates osteoclastogenesis in RAW264.7 cells","volume":"279","author":"Hirotani","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/jcb.20048","article-title":"Expression of nox4 in osteoclasts","volume":"92","author":"Yang","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2152\/jmi.56.33","article-title":"NADPH oxidase-derived reactive oxygen species are essential for differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts","volume":"56","author":"Sasaki","year":"2009","journal-title":"J. Med. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1749-6632.2009.05377.x","article-title":"Role of Mitochondrial Reactive Oxygen Species in Osteoclast Differentiation","volume":"Volume 1192","author":"Srinivasan","year":"2010","journal-title":"Proceedings of the Annals of the New York Academy of Sciences"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35209","DOI":"10.1074\/jbc.M505815200","article-title":"Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation-induced cytokine-mediated osteoclastogenesis","volume":"280","author":"Kim","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1038\/emboj.2009.239","article-title":"FoxM1, a critical regulator of oxidative stress during oncogenesis","volume":"28","author":"Park","year":"2009","journal-title":"EMBO J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/ncb1217","article-title":"FoxM1 is required for execution of the mitotic programme and chromosome stability","volume":"7","author":"Laoukili","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10875","DOI":"10.1128\/MCB.25.24.10875-10894.2005","article-title":"Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase","volume":"25","author":"Wang","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.semcancer.2017.11.018","article-title":"The FOXO3-FOXM1 axis: A key cancer drug target and a modulator of cancer drug resistance","volume":"50","author":"Yao","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1158\/1541-7786.MCR-11-0559","article-title":"The p38 MAPK-MK2 axis regulates E2F1 and FOXM1 expression after epirubicin treatment","volume":"10","author":"Koo","year":"2012","journal-title":"Mol. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1038\/onc.2009.436","article-title":"phenotype-assisted transcriptome analysis identifies FOXM1 downstream from Ras-MKK3-p38 to Regulate in vitro cellular invasion","volume":"29","author":"Behren","year":"2010","journal-title":"Oncogene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1210\/en.2014-1334","article-title":"The sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice","volume":"155","author":"Artsi","year":"2014","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"19385","DOI":"10.1074\/jbc.M702452200","article-title":"Forkhead proteins are critical for bone morphogenetic protein-2 regulation and anti-tumor activity of resveratrol","volume":"282","author":"Su","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_24","first-page":"3646","article-title":"Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat","volume":"25","author":"Momken","year":"2011","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1210\/me.2015-1133","article-title":"Sirtuin1 suppresses osteoclastogenesis by deacetylating FoxOs","volume":"29","author":"Kim","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/acel.12220","article-title":"SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass","volume":"13","author":"Mercken","year":"2014","journal-title":"Aging Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cmet.2008.06.011","article-title":"Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span","volume":"8","author":"Pearson","year":"2008","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9943","DOI":"10.1158\/0008-5472.CAN-05-0651","article-title":"Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation","volume":"65","author":"Boissy","year":"2005","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.bbrc.2010.09.053","article-title":"Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ros production","volume":"401","author":"He","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11492","DOI":"10.1074\/jbc.M110.198713","article-title":"Resveratrol-mediated SIRT-1 interactions with P300 modulate receptor activator of NF-KappaB ligand (RANKL) activation of NF-KappaB signaling and inhibit osteoclastogenesis in bone-derived cells","volume":"286","author":"Shakibaei","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejphar.2008.06.067","article-title":"Resveratrol protects primary rat hepatocytes against oxidative stress damage: Activation of the Nrf2 transcription factor and augmented activities of antioxidant enzymes","volume":"591","author":"Rubiolo","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1124\/mol.109.058479","article-title":"Resveratrol protects mitochondria against oxidative stress through AMP-activated protein kinase-mediated glycogen synthase kinase-3beta inhibition downstream of poly(ADP-ribose)polymerase-LKB1 pathway","volume":"76","author":"Shin","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Miura, S., Saitoh, S.I., Kokubun, T., Owada, T., Yamauchi, H., Machii, H., and Takeishi, Y. (2017). Mitochondrial-targeted antioxidant maintains blood flow, mitochondrial function, and redox balance in old mice following prolonged limb ischemia. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091897"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.freeradbiomed.2015.11.013","article-title":"Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy","volume":"90","author":"Ni","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"38014","DOI":"10.1038\/srep38014","article-title":"NADPH oxidase gp91(phox) contributes to RANKL-induced osteoclast differentiation by upregulating NFATc1","volume":"6","author":"Kang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Agidigbi, T.S., and Kim, C. (2019). Reactive oxygen species in osteoclast differentiation and possible pharmaceutical targets of ros-mediated osteoclast diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143576"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2147\/HP.S95960","article-title":"Hypoxic Regulation of Osteoclast Differentiation and Bone Resorption Activity","volume":"3","author":"Knowles","year":"2015","journal-title":"Hypoxia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"188","DOI":"10.4093\/dmj.2015.39.3.188","article-title":"Pyruvate dehydrogenase kinases: Therapeutic targets for diabetes and cancers","volume":"39","author":"Jeoung","year":"2015","journal-title":"Diabetes Metab. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"654198","DOI":"10.1155\/2014\/654198","article-title":"Mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes","volume":"2014","author":"He","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rana, T., Chakrabarti, A., Freeman, M., and Biswas, S. (2013). Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGF\u03b2. PLoS ONE, 8.","DOI":"10.1371\/annotation\/95cefb34-2f3d-42a5-b73e-53c531591f0b"},{"key":"ref_41","first-page":"5640","article-title":"Doxorubicin restrains osteogenesis and promotes osteoclastogenesis in vitro","volume":"12","author":"Zhou","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"804","DOI":"10.2319\/072418-536.1","article-title":"Force-induced decline of FOXM1 in human periodontal ligament cells contributes to osteoclast differentiation","volume":"89","author":"Li","year":"2019","journal-title":"Angle Orthod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"dev181834","DOI":"10.1242\/dev.181834","article-title":"Unique and non-redundant function of csf1r paralogues in regulation and evolution of post-embryonic development of the zebrafish","volume":"147","author":"Henke","year":"2020","journal-title":"Development"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ajpath.2013.03.012","article-title":"Combination of oxidative stress and foxm1 inhibitors induces apoptosis in cancer cells and inhibits xenograft tumor growth","volume":"183","author":"Halasi","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6471","DOI":"10.1038\/ncomms7471","article-title":"Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia","volume":"6","author":"Buchner","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/mrd.22042","article-title":"The importance of mitochondrial metabolic activity and mitochondrial dna replication during oocyte maturation in vitro on oocyte quality and subsequent embryo developmental competence","volume":"79","author":"Ge","year":"2012","journal-title":"Mol. Reprod. Dev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Le Gal, K., Wiel, C., Ibrahim, M.X., Henricsson, M., Sayin, V.I., and Bergo, M.O. (2021). Mitochondria-targeted antioxidants MitoQ and MitoTEMPO do not influence BRAF-driven malignant melanoma and KRAS-driven lung cancer progression in mice. Antioxidants, 10.","DOI":"10.3390\/antiox10020163"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1084\/jem.20050645","article-title":"DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells","volume":"202","author":"Yagi","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature01960","article-title":"Small molecule activators of sirtuins extend saccharomyces cerevisiae lifespan","volume":"425","author":"Howitz","year":"2003","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14138","DOI":"10.1073\/pnas.94.25.14138","article-title":"Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor","volume":"94","author":"Gehm","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7829","DOI":"10.1073\/pnas.130200197","article-title":"Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression","volume":"97","author":"Shevde","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.molcel.2009.04.033","article-title":"The Nfkb1 and Nfkb2 proteins P105 and P100 function as the core of high-molecular-weight heterogeneous complexes","volume":"34","author":"Savinova","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1038\/sj.emboj.7600244","article-title":"Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase","volume":"23","author":"Yeung","year":"2004","journal-title":"EMBO J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6913","DOI":"10.1074\/jbc.M109.051557","article-title":"RANKL-mediated reactive oxygen species pathway that induces long lasting Ca2+ oscillations essential for osteoclastogenesis","volume":"285","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.biopsycho.2004.11.007","article-title":"The relationship between fatigue and quality of life and inflammation during anthracycline-based chemotherapy in breast cancer","volume":"69","author":"Mills","year":"2005","journal-title":"Biol. Psychol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kodama, J., and Kaito, T. (2020). Osteoclast multinucleation: Review of current literature. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165685"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3389\/fcell.2020.00433","article-title":"Cathepsin K: The action in and beyond bone","volume":"8","author":"Dai","year":"2020","journal-title":"Front. cell Dev. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1124\/jpet.106.103465","article-title":"Role of matrix metalloproteinases in intestinal inflammation","volume":"318","author":"Medina","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1365-2249.2006.03188.x","article-title":"Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo","volume":"146","author":"Menzel","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/path.3009","article-title":"V Severity of doxorubicin-induced small intestinal mucositis is regulated by the TLR-2 and TLR-9 pathways","volume":"226","author":"Kaczmarek","year":"2012","journal-title":"J. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1093\/sleep\/32.9.1155","article-title":"Breast cancer patients have progressively impaired sleep-wake activity rhythms during chemotherapy","volume":"32","author":"Savard","year":"2009","journal-title":"Sleep"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.slsci.2016.10.006","article-title":"Sleep pattern and locomotor activity are impaired by doxorubicin in non-tumor-bearing rats","volume":"9","author":"Lira","year":"2016","journal-title":"Sleep Sci."},{"key":"ref_63","first-page":"959","article-title":"Longitudinal prospective assessment of sleep quality: Before, during, and after adjuvant chemotherapy for breast cancer","volume":"21","author":"Sanford","year":"2013","journal-title":"Support. Care Cancer Off. J. Multinatl. Assoc. Support. Care Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1177\/7.1.39","article-title":"histochemical demonstration of acid phosphatase activity in osteoclasts","volume":"7","author":"Burstone","year":"1959","journal-title":"J. Histochem. Cytochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00441-003-0830-1","article-title":"Development of two bone-derived cell lines from the marine teleost sparus aurata; evidence for extracellular matrix mineralization and cell-type-specific expression of matrix Gla protein and osteocalcin","volume":"315","author":"Pombinho","year":"2004","journal-title":"Cell Tissue Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1439-0426.2012.01994.x","article-title":"Polyunsaturated fatty acids regulate cell proliferation, extracellular matrix mineralization and gene expression in a gilthead seabream skeletal cell line","volume":"28","author":"Viegas","year":"2012","journal-title":"J. Appl. 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