{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:27:25Z","timestamp":1780374445644,"version":"3.54.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T00:00:00Z","timestamp":1459382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T00:00:00Z","timestamp":1459382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Dihydroartemisinin (DHA) is a widely used antimalarial drug isolated from the plant <jats:italic>Artemisia annua<\/jats:italic>. Recent studies suggested that DHA has antitumor effects utilizing its reactive oxygen species (ROS) yielding mechanism. Here, we reported that DHA is inhibitory on lipopolysaccharide (LPS)-induced osteoclast (OC) differentiation, fusion and bone-resorption activity <jats:italic>in vitro<\/jats:italic>. Intracellular ROS detection revealed that DHA could remarkably increase ROS accumulation during LPS-induced osteoclastogenesis. Moreover, cell apoptosis was also increased by DHA treatment. We found that DHA-activated caspase-3 increased Bax\/Bcl-2 ratio during LPS-induced osteoclastogenesis. Meanwhile, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome <jats:italic>c<\/jats:italic> from the mitochondria into the cytosol were observed, indicating that ROS-mediated mitochondrial dysfunction is crucial in DHA-induced apoptosis during LPS-induced osteoclastogenesis. <jats:italic>In vivo<\/jats:italic> study showed that DHA treatment decreased OC number, prevents bone loss, rescues bone microarchitecture and restores bone strength in LPS-induced bone-loss mouse model. Together, our findings indicate that DHA is protective against LPS-induced bone loss through apoptosis induction of osteoclasts via ROS accumulation and the mitochondria-dependent apoptosis pathway. Therefore, DHA may be considered as a new therapeutic candidate for treating inflammatory bone loss.<\/jats:p>","DOI":"10.1038\/cddis.2016.69","type":"journal-article","created":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T13:02:47Z","timestamp":1459429367000},"page":"e2162-e2162","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Dihydroartemisinin attenuates lipopolysaccharide-induced osteoclastogenesis and bone loss via the mitochondria-dependent apoptosis pathway"],"prefix":"10.1038","volume":"7","author":[{"given":"C","family":"Dou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,31]]},"reference":[{"key":"BFcddis201669_CR1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature01658","volume":"423","author":"WJ Boyle","year":"2003","unstructured":"Boyle WJ, Simonet WS, Lacey DL . Osteoclast differentiation and activation. Nature 2003; 423: 337\u2013342.","journal-title":"Nature"},{"key":"BFcddis201669_CR2","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1196\/annals.1365.035","volume":"1092","author":"DJ Hadjidakis","year":"2006","unstructured":"Hadjidakis DJ, Androulakis II . Bone remodeling. Ann N Y Acad Sci 2006; 1092: 385\u2013396.","journal-title":"Ann N Y Acad Sci"},{"key":"BFcddis201669_CR3","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1126\/science.289.5484.1508","volume":"289","author":"GA Rodan","year":"2000","unstructured":"Rodan GA, Martin TJ . Therapeutic approaches to bone diseases. Science 2000; 289: 1508\u20131514.","journal-title":"Science"},{"key":"BFcddis201669_CR4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","volume":"93","author":"DL Lacey","year":"1998","unstructured":"Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93: 165\u2013176.","journal-title":"Cell"},{"key":"BFcddis201669_CR5","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1084\/jem.190.12.1741","volume":"190","author":"F Arai","year":"1999","unstructured":"Arai F, Miyamoto T, Ohneda O, Inada T, Sudo T, Brasel K et al. Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J Exp Med 1999; 190: 1741\u20131754.","journal-title":"J Exp Med"},{"key":"BFcddis201669_CR6","first-page":"308","volume":"17","author":"GD Roodman","year":"1996","unstructured":"Roodman GD . Advances in bone biology: the osteoclast. Endocr Rev 1996; 17: 308\u2013332.","journal-title":"Endocr Rev"},{"key":"BFcddis201669_CR7","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","volume":"289","author":"SL Teitelbaum","year":"2000","unstructured":"Teitelbaum SL . Bone resorption by osteoclasts. Science 2000; 289: 1504\u20131508.","journal-title":"Science"},{"key":"BFcddis201669_CR8","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.tim.2003.10.005","volume":"11","author":"B Henderson","year":"2003","unstructured":"Henderson B, Nair SP . Hard labour: bacterial infection of the skeleton. Trends Microbiol 2003; 11: 570\u2013577.","journal-title":"Trends Microbiol"},{"key":"BFcddis201669_CR9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1600-0757.2006.00185.x","volume":"43","author":"T Nagasawa","year":"2007","unstructured":"Nagasawa T, Kiji M, Yashiro R, Hormdee D, Lu H, Kunze M et al. Roles of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin in periodontal health and disease. Periodontol 2000 2007; 43: 65\u201384.","journal-title":"Periodontol 2000"},{"key":"BFcddis201669_CR10","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1128\/iai.64.7.2371-2380.1996","volume":"64","author":"SP Nair","year":"1996","unstructured":"Nair SP, Meghji S, Wilson M, Reddi K, White P, Henderson B . Bacterially induced bone destruction: mechanisms and misconceptions. Infect Immunity 1996; 64: 2371\u20132380.","journal-title":"Infect Immunity"},{"key":"BFcddis201669_CR11","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1002\/jnr.20180","volume":"77","author":"S Pawate","year":"2004","unstructured":"Pawate S, Shen Q, Fan F, Bhat NR . Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma. J Neurosci Res 2004; 77: 540\u2013551.","journal-title":"J Neurosci Res"},{"key":"BFcddis201669_CR12","doi-asserted-by":"publisher","first-page":"C1586","DOI":"10.1152\/ajpcell.00129.2008","volume":"294","author":"J Sun","year":"2008","unstructured":"Sun J, Ramnath RD, Zhi L, Tamizhselvi R, Bhatia M . Substance P enhances NF-kappaB transactivation and chemokine response in murine macrophages via ERK1\/2 and p38 MAPK signaling pathways. Am J Physiol Cell Physiol 2008; 294: C1586\u2013C1596.","journal-title":"Am J Physiol Cell Physiol"},{"key":"BFcddis201669_CR13","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1172\/JCI114485","volume":"85","author":"IR Garrett","year":"1990","unstructured":"Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR . Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 1990; 85: 632\u2013639.","journal-title":"J Clin Invest"},{"key":"BFcddis201669_CR14","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.yexcr.2004.07.035","volume":"301","author":"H Ha","year":"2004","unstructured":"Ha H, Kwak HB, Lee SW, Jin HM, Kim HM, Kim HH et al. Reactive oxygen species mediate RANK signaling in osteoclasts. Exp Cell Res 2004; 301: 119\u2013127.","journal-title":"Exp Cell Res"},{"key":"BFcddis201669_CR15","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1182\/blood-2004-09-3662","volume":"106","author":"NK Lee","year":"2005","unstructured":"Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS et al. A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood 2005; 106: 852\u2013859.","journal-title":"Blood"},{"key":"BFcddis201669_CR16","doi-asserted-by":"publisher","first-page":"6427","DOI":"10.4049\/jimmunol.169.11.6427","volume":"169","author":"NY Bhatt","year":"2002","unstructured":"Bhatt NY, Kelley TW, Khramtsov VV, Wang Y, Lam GK, Clanton TL et al. Macrophage-colony-stimulating factor-induced activation of extracellular-regulated kinase involves phosphatidylinositol 3-kinase and reactive oxygen species in human monocytes. J Immunol 2002; 169: 6427\u20136434.","journal-title":"J Immunol"},{"key":"BFcddis201669_CR17","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.1038\/ncomms4773","volume":"5","author":"SM Bartell","year":"2014","unstructured":"Bartell SM, Kim HN, Ambrogini E, Han L, Iyer S, Serra Ucer S et al. FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation. Nat Commun 2014; 5: 3773.","journal-title":"Nat Commun"},{"key":"BFcddis201669_CR18","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1089\/ars.2013.5748","volume":"22","author":"H Park","year":"2015","unstructured":"Park H, Noh AL, Kang JH, Sim JS, Lee DS, Yim M . Peroxiredoxin II negatively regulates lipopolysaccharide-induced osteoclast formation and bone loss via JNK and STAT3. Antioxidants Redox Signal 2015; 22: 63\u201377.","journal-title":"Antioxidants Redox Signal"},{"key":"BFcddis201669_CR19","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/aps.2012.104","volume":"33","author":"Y Li","year":"2012","unstructured":"Li Y . Qinghaosu (artemisinin): chemistry and pharmacology. Acta Pharmacol Sin 2012; 33: 1141\u20131146.","journal-title":"Acta Pharmacol Sin"},{"key":"BFcddis201669_CR20","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.tips.2008.07.004","volume":"29","author":"S Krishna","year":"2008","unstructured":"Krishna S, Bustamante L, Haynes RK, Staines HM . Artemisinins: their growing importance in medicine. Trends Pharmacol Sci 2008; 29: 520\u2013527.","journal-title":"Trends Pharmacol Sci"},{"key":"BFcddis201669_CR21","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3892\/ijmm.2012.1176","volume":"31","author":"H Mao","year":"2013","unstructured":"Mao H, Gu H, Qu X, Sun J, Song B, Gao W et al. Involvement of the mitochondrial pathway and Bim\/Bcl-2 balance in dihydroartemisinin-induced apoptosis in human breast cancer in vitro. Int J Mol Med 2013; 31: 213\u2013218.","journal-title":"Int J Mol Med"},{"key":"BFcddis201669_CR22","doi-asserted-by":"publisher","first-page":"819","DOI":"10.4161\/cbt.9.10.11552","volume":"9","author":"Q He","year":"2010","unstructured":"He Q, Shi J, Shen XL, An J, Sun H, Wang L et al. Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells. Cancer Biol Ther 2010; 9: 819\u2013824.","journal-title":"Cancer Biol Ther"},{"key":"BFcddis201669_CR23","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.freeradbiomed.2004.06.023","volume":"37","author":"T Efferth","year":"2004","unstructured":"Efferth T, Benakis A, Romero MR, Tomicic M, Rauh R, Steinbach D et al. Enhancement of cytotoxicity of artemisinins toward cancer cells by ferrous iron. Free Radical Biol Med 2004; 37: 998\u20131009.","journal-title":"Free Radical Biol Med"},{"key":"BFcddis201669_CR24","doi-asserted-by":"publisher","first-page":"407","DOI":"10.2174\/138945006776359412","volume":"7","author":"T Efferth","year":"2006","unstructured":"Efferth T . Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr Drug Targets 2006; 7: 407\u2013421.","journal-title":"Curr Drug Targets"},{"key":"BFcddis201669_CR25","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S0300-9084(03)00129-9","volume":"85","author":"G Roue","year":"2003","unstructured":"Roue G, Bitton N, Yuste VJ, Montange T, Rubio M, Dessauge F et al. Mitochondrial dysfunction in CD47-mediated caspase-independent cell death: ROS production in the absence of cytochrome c and AIF release. Biochimie 2003; 85: 741\u2013746.","journal-title":"Biochimie"},{"key":"BFcddis201669_CR26","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/sj.cdd.4401950","volume":"13","author":"C Garrido","year":"2006","unstructured":"Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G . Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 2006; 13: 1423\u20131433.","journal-title":"Cell Death Differ"},{"key":"BFcddis201669_CR27","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1007\/s10637-010-9481-8","volume":"29","author":"JJ Lu","year":"2011","unstructured":"Lu JJ, Chen SM, Zhang XW, Ding J, Meng LH . The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest New Drugs 2011; 29: 1276\u20131283.","journal-title":"Invest New Drugs"},{"key":"BFcddis201669_CR28","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1097\/CAD.0b013e3283212ade","volume":"20","author":"H Chen","year":"2009","unstructured":"Chen H, Sun B, Pan S, Jiang H, Sun X . Dihydroartemisinin inhibits growth of pancreatic cancer cells in vitro and in vivo. Anticancer Drugs 2009; 20: 131\u2013140.","journal-title":"Anticancer Drugs"},{"key":"BFcddis201669_CR29","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1111\/j.1582-4934.2008.00360.x","volume":"13","author":"T Chen","year":"2009","unstructured":"Chen T, Li M, Zhang R, Wang H . Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy. J Cell Mol Med 2009; 13: 1358\u20131370.","journal-title":"J Cell Mol Med"},{"key":"BFcddis201669_CR30","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.3390\/molecules15031705","volume":"15","author":"PM O'Neill","year":"2010","unstructured":"O'Neill PM, Barton VE, Ward SA . The molecular mechanism of action of artemisinin\u2014the debate continues. Molecules 2010; 15: 1705\u20131721.","journal-title":"Molecules"},{"key":"BFcddis201669_CR31","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1096\/fasebj.11.2.9039953","volume":"11","author":"HM Lander","year":"1997","unstructured":"Lander HM . An essential role for free radicals and derived species in signal transduction. FASEB J 1997; 11: 118\u2013124.","journal-title":"FASEB J"},{"key":"BFcddis201669_CR32","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.bbrc.2010.09.053","volume":"401","author":"X He","year":"2010","unstructured":"He X, Andersson G, Lindgren U, Li Y . Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production. Biochem Biophys Res Commun 2010; 401: 356\u2013362.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFcddis201669_CR33","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.bbrc.2012.01.005","volume":"418","author":"HJ Moon","year":"2012","unstructured":"Moon HJ, Ko WK, Han SW, Kim DS, Hwang YS, Park HK et al. Antioxidants, like coenzyme Q10, selenite, and curcumin, inhibited osteoclast differentiation by suppressing reactive oxygen species generation. Biochem Biophys Res Commun 2012; 418: 247\u2013253.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFcddis201669_CR34","doi-asserted-by":"publisher","first-page":"e93696","DOI":"10.1371\/journal.pone.0093696","volume":"9","author":"R Sharma","year":"2014","unstructured":"Sharma R, Callaway D, Vanegas D, Bendele M, Lopez-Cruzan M, Horn D et al. Caspase-2 maintains bone homeostasis by inducing apoptosis of oxidatively-damaged osteoclasts. PLoS One 2014; 9: e93696.","journal-title":"PLoS One"},{"key":"BFcddis201669_CR35","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/jcp.10041","volume":"190","author":"K Suda","year":"2002","unstructured":"Suda K, Woo JT, Takami M, Sexton PM, Nagai K . Lipopolysaccharide supports survival and fusion of preosteoclasts independent of TNF-alpha, IL-1, and RANKL. J Cell Physiol 2002; 190: 101\u2013108.","journal-title":"J Cell Physiol"},{"key":"BFcddis201669_CR36","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s00018-014-1712-2","volume":"72","author":"K Schroder","year":"2015","unstructured":"Schroder K . NADPH oxidases in bone homeostasis and osteoporosis. Cell Mol Life Sci 2015; 72: 25\u201338.","journal-title":"Cell Mol Life Sci"},{"key":"BFcddis201669_CR37","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.cell.2005.02.001","volume":"120","author":"RS Balaban","year":"2005","unstructured":"Balaban RS, Nemoto S, Finkel T . Mitochondria, oxidants, and aging. Cell 2005; 120: 483\u2013495.","journal-title":"Cell"},{"key":"BFcddis201669_CR38","first-page":"2922","volume":"15","author":"X Wang","year":"2001","unstructured":"Wang X . The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15: 2922\u20132933.","journal-title":"Genes Dev"},{"key":"BFcddis201669_CR39","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1177\/1753425914524242","volume":"21","author":"E Odkhuu","year":"2015","unstructured":"Odkhuu E, Koide N, Tsolmongyn B, Jambalganiin U, Naiki Y, Komatsu T et al. Involvement of redox balance in in vitro osteoclast formation of RAW 264.7 macrophage cells in response to LPS. Innate Immun 2015; 21: 194\u2013202.","journal-title":"Innate Immun"},{"key":"BFcddis201669_CR40","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1007\/s10637-011-9676-7","volume":"30","author":"CM Cabello","year":"2012","unstructured":"Cabello CM, Lamore SD, Bair WB 3rd, Qiao S, Azimian S, Lesson JL et al. The redox antimalarial dihydroartemisinin targets human metastatic melanoma cells but not primary melanocytes with induction of NOXA-dependent apoptosis. Invest New Drugs 2012; 30: 1289\u20131301.","journal-title":"Invest New Drugs"},{"key":"BFcddis201669_CR41","doi-asserted-by":"crossref","unstructured":"Zhou L, Liu Q, Yang M, Wang T, Yao J, Cheng J et al. Dihydroartemisinin, an anti-malaria drug, suppresses estrogen deficiency-induced osteoporosis, osteoclast formation and RANKL induced signalling pathways. J Bone Miner Res 2015 (e-pub ahead of print; doi:10.1002\/jbmr.2771).","DOI":"10.1002\/jbmr.2771"},{"key":"BFcddis201669_CR42","doi-asserted-by":"publisher","first-page":"19074","DOI":"10.1038\/srep19074","volume":"6","author":"MX Feng","year":"2016","unstructured":"Feng MX, Hong JX, Wang Q, Fan YY, Yuan CT, Lei XH et al. Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts. Sci Rep 2016; 6: 19074.","journal-title":"Sci Rep"},{"key":"BFcddis201669_CR43","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.bbagrm.2014.08.002","volume":"1839","author":"C Dou","year":"2014","unstructured":"Dou C, Zhang C, Kang F, Yang X, Jiang H, Bai Y et al. MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation. Biochim Biophys Acta 2014; 1839: 1084\u20131096.","journal-title":"Biochim Biophys Acta"},{"key":"BFcddis201669_CR44","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1002\/jcp.24916","volume":"231","author":"C Dou","year":"2016","unstructured":"Dou C, Li J, Kang F, Cao Z, Yang X, Jiang H et al. Dual effect of cyanidin on RANKL-induced differentiation and fusion of osteoclasts. J Cell Physiol 2016; 231: 558\u2013567.","journal-title":"J Cell Physiol"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis201669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis201669","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis201669.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T09:04:23Z","timestamp":1672823063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis201669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,31]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3]]}},"alternative-id":["BFcddis201669"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.69","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,31]]},"assertion":[{"value":"7 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 March 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}