{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:42:23Z","timestamp":1783629743689,"version":"3.55.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Dalian Medical Science Research Project","award":["1911095"],"award-info":[{"award-number":["1911095"]}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81870763"],"award-info":[{"award-number":["81870763"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Beijing","award":["7192073"],"award-info":[{"award-number":["7192073"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Oral Health"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Granulocyte colony-stimulating factor (G-CSF) is an important immune factor that mediates bone metabolism by regulating the functions of osteoclasts and osteoblasts. Bone loss is a serious and progressive result of periodontitis. However, the mechanisms underlying the effects of G-CSF on periodontal inflammation have yet not been completely elucidated. Here, we examined whether an anti-G-CSF antibody could inhibit bone resorption in a model of experimental periodontitis and investigated the local expression of G-CSF in periodontal tissues.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Experimental periodontitis was induced in mice using ligatures. The levels of G-CSF in serum and bone marrow were measured; immunofluorescence was then performed to analyze the localization and expression of G-CSF in periodontal tissues. Mice with periodontitis were administered anti-G-CSF antibody by tail vein injection to assess the inhibition of bone resorption. Three-dimensional reconstruction was performed to measure bone destruction\u2010related parameters via micro-computed tomography analysis. Immunofluorescence staining was used to investigate the presence of osteocalcin-positive osteoblasts; tartrate-resistant acid phosphatase (TRAP) staining was used to observe osteoclast activity in alveolar bone.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The level of G-CSF in serum was significantly elevated in mice with periodontitis. Immunofluorescence analyses showed that G-CSF was mostly expressed in the cell membrane of gingival epithelial cells; this expression was enhanced in the periodontitis group. Additionally, systemic administration of anti-G-CSF antibody significantly inhibited alveolar bone resorption, as evidenced by improvements in bone volume\/total volume, bone surface area\/bone volume, trabecular thickness, trabecular spacing, and trabecular pattern factor values. Immunofluorescence analysis revealed an enhanced number of osteocalcin-positive osteoblasts, while TRAP staining revealed reduction of osteoclast activity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>G-CSF expression levels were significantly up-regulated in the serum and gingival epithelial cells. Together, anti-G-CSF antibody administration could alleviates alveolar bone resorption, suggesting that G-CSF may be one of the essential immune factors that mediate the bone loss in periodontitis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12903-021-01658-1","type":"journal-article","created":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T04:02:46Z","timestamp":1623470566000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Granulocyte colony-stimulating factor (G-CSF) mediates bone resorption in periodontitis"],"prefix":"10.1186","volume":"21","author":[{"given":"Hui","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuomin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,12]]},"reference":[{"issue":"11","key":"1658_CR1","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1177\/0022034514552491","volume":"93","author":"NJ Kassebaum","year":"2014","unstructured":"Kassebaum NJ, Bernabe E, Dahiya M, Bhandari B, Murray CJL, Marcenes W. Global burden of severe periodontitis in 1990\u20132010: a systematic review and meta-regression. J Dent Res. 2014;93(11):1045\u201353.","journal-title":"J Dent Res"},{"issue":"8","key":"1658_CR2","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.3390\/jcm8081135","volume":"8","author":"E Knnen","year":"2019","unstructured":"Knnen E, Gursoy M, Gursoy UK. Periodontitis: a multifaceted disease of tooth-supporting tissues. J Clin Med. 2019;8(8):1135.","journal-title":"J Clin Med"},{"issue":"7","key":"1658_CR3","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nrmicro2337","volume":"8","author":"RP Darveau","year":"2010","unstructured":"Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010;8(7):481\u201390.","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"1658_CR4","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.jmii.2016.04.007","volume":"51","author":"C Tsai","year":"2018","unstructured":"Tsai C, Tang CY, Tan T, Chen K, Liao K, Liou M. Subgingival microbiota in individuals with severe chronic periodontitis. J Microbiol Immunol Infect. 2018;51(2):226\u201334.","journal-title":"J Microbiol Immunol Infect"},{"issue":"1","key":"1658_CR5","doi-asserted-by":"publisher","first-page":"1538927","DOI":"10.1080\/20002297.2018.1538927","volume":"11","author":"S Elmanfi","year":"2019","unstructured":"Elmanfi S, Zhou J, Sintim HO, K\u00f6n\u00f6nen E, G\u00fcrsoy M, G\u00fcrsoy UK. Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides. J Oral Microbiol. 2019;11(1):1538927.","journal-title":"J Oral Microbiol"},{"issue":"6812","key":"1658_CR6","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/35046196","volume":"408","author":"JR Arron","year":"2000","unstructured":"Arron JR, Choi Y. Bone versus immune system. Nature. 2000;408(6812):535\u20136.","journal-title":"Nature"},{"issue":"12","key":"1658_CR7","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1111\/jcpe.12781","volume":"44","author":"J Meyle","year":"2017","unstructured":"Meyle J, Dommisch H, Groeger S, Giacaman RA, Costalonga M, Herzberg M. The innate host response in caries and periodontitis. J Clin Periodontol. 2017;44(12):1215\u201325.","journal-title":"J Clin Periodontol"},{"issue":"1","key":"1658_CR8","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1177\/0022034514526240","volume":"26","author":"G Hajishengallis","year":"2014","unstructured":"Hajishengallis G, Sahingur SE. Novel inflammatory pathways in periodontitis. Adv Dent Res. 2014;26(1):23\u20139.","journal-title":"Adv Dent Res"},{"issue":"1","key":"1658_CR9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/prd.12146","volume":"76","author":"S Kurgan","year":"2018","unstructured":"Kurgan S, Kantarci A. Molecular basis for immunohistochemical and inflammatory changes during progression of gingivitis to periodontitis. Periodontol 2000. 2018;76(1):51\u201367.","journal-title":"Periodontol 2000"},{"issue":"9\u201310","key":"1658_CR10","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1007\/s12033-017-0026-7","volume":"59","author":"G Mickiene","year":"2017","unstructured":"Mickiene G, Dalgediene I, Dapkunas Z, Zvirblis G, Pesliakas H, Kaupinis A, et al. Construction, purification, and characterization of a homodimeric granulocyte colony-stimulating factor. Mol Biotechnol. 2017;59(9\u201310):374\u201384.","journal-title":"Mol Biotechnol"},{"issue":"1","key":"1658_CR11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1590\/S0103-64402008000100001","volume":"19","author":"AC Queiroz","year":"2008","unstructured":"Queiroz AC, Taba M Jr, O\u2019Connell PA, N\u00f3brega PB, Costa PP, Kawata VKS, et al. Inflammation markers in healthy and periodontitis patients: a preliminary data screening. Braz Dent J. 2008;19(1):3\u20138.","journal-title":"Braz Dent J"},{"issue":"4","key":"1658_CR12","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3816\/SCT.2006.n.020","volume":"3","author":"DC Dale","year":"2006","unstructured":"Dale DC, Bolyard AA, Schwinzer BG, Pracht G, Bonilla MA, Boxer L, et al. The severe chronic neutropenia international registry: 10-year follow-up report. Support Cancer Ther. 2006;3(4):220\u201331.","journal-title":"Support Cancer Ther"},{"issue":"11","key":"1658_CR13","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1359\/jbmr.080612","volume":"23","author":"MJ Christopher","year":"2008","unstructured":"Christopher MJ, Link DC. Granulocyte colony-stimulating factor induces osteoblast apoptosis and inhibits osteoblast differentiation. J Bone Miner Res. 2008;23(11):1765\u201374.","journal-title":"J Bone Miner Res"},{"issue":"6","key":"1658_CR14","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/j.immuni.2016.05.012","volume":"44","author":"A Terashima","year":"2016","unstructured":"Terashima A, Okamoto K, Nakashima T, Akira S, Ikuta K, Takayanagi H. Sepsis-induced osteoblast ablation causes immunodeficiency. Immunity. 2016;44(6):1434\u201343.","journal-title":"Immunity"},{"key":"1658_CR15","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.molimm.2019.11.003","volume":"117","author":"Z Zhang","year":"2020","unstructured":"Zhang Z, Yuan W, Deng J, Wang D, Zhang T, Peng L, et al. Granulocyte colony stimulating factor (G-CSF) regulates neutrophils infiltration and periodontal tissue destruction in an experimental periodontitis. Mol Immunol. 2020;117:110\u201321.","journal-title":"Mol Immunol"},{"issue":"1\u20132","key":"1658_CR16","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.jim.2013.05.002","volume":"394","author":"T Abe","year":"2013","unstructured":"Abe T, Hajishengallis G. Optimization of the ligature-induced periodontitis model in mice. J Immunol Methods. 2013;394(1\u20132):49\u201354.","journal-title":"J Immunol Methods"},{"issue":"6","key":"1658_CR17","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1016\/j.ajpath.2016.02.001","volume":"186","author":"CA Parkos","year":"2016","unstructured":"Parkos CA. Neutrophil-epithelial interactions: a double-edged sword. Am J Pathol. 2016;186(6):1404\u201316.","journal-title":"Am J Pathol"},{"key":"1658_CR18","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jri.2015.01.010","volume":"108","author":"W Wuerfel","year":"2015","unstructured":"Wuerfel W. Treatment with granulocyte colony-stimulating factor in patients with repetitive implantation failures and\/or recurrent spontaneous abortions. J Reprod Immunol. 2015;108:123\u201335.","journal-title":"J Reprod Immunol"},{"issue":"4","key":"1658_CR19","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S1074-7613(02)00424-7","volume":"17","author":"CL Semerad","year":"2002","unstructured":"Semerad CL, Liu F, Gregory AD, Stumpf K, Link DC. G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood. Immunity. 2002;17(4):413\u201323.","journal-title":"Immunity"},{"issue":"8","key":"1658_CR20","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1080\/00016357.2017.1372623","volume":"75","author":"HRZ Elabdeen","year":"2017","unstructured":"Elabdeen HRZ, Mustafa M, Ali R, Bolstad A. Cytokine profile in gingival crevicular fluid and plasma of patients with aggressive periodontitis. Acta Odontol Scand. 2017;75(8):616\u201322.","journal-title":"Acta Odontol Scand"},{"issue":"2","key":"1658_CR21","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1177\/0961203318819134","volume":"28","author":"MRC Sete","year":"2019","unstructured":"Sete MRC, Carlos JC, Lirajunior R, Bostr\u00f6m EA, Sztajnbok FR, Figueredo CM. Clinical, immunological and microbial gingival profile of juvenile systemic lupus erythematosus patients. Lupus. 2019;28(2):189\u201398.","journal-title":"Lupus"},{"issue":"4","key":"1658_CR22","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1111\/cts.12467","volume":"10","author":"S Li","year":"2017","unstructured":"Li S, Chen Y, Qiu L, Qin M. G-CSF indirectly induces apoptosis of osteoblasts during hematopoietic stem cell mobilization. Clin Transl Sci. 2017;10(4):287\u201391.","journal-title":"Clin Transl Sci"},{"issue":"12","key":"1658_CR23","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1042\/CS20181001","volume":"133","author":"Y Hou","year":"2019","unstructured":"Hou Y, Qin H, Jiang N, Liu G, Wu H, Bai L, et al. G-CSF partially mediates bone loss induced by Staphylococcus aureus infection in mice. Clin Sci. 2019;133(12):1297\u2013308.","journal-title":"Clin Sci"},{"issue":"8","key":"1658_CR24","doi-asserted-by":"publisher","first-page":"e776","DOI":"10.1097\/SCS.0000000000005769","volume":"30","author":"J Zhao","year":"2019","unstructured":"Zhao J, Zhao Q, Ning P, Shang K, Liu C, Ni M, et al. G-CSF inhibits growths of osteoblasts and osteocytes by upregulating nitric oxide production in neutrophils. J Craniofac Surg. 2019;30(8):e776\u201380.","journal-title":"J Craniofac Surg"},{"issue":"5","key":"1658_CR25","first-page":"418","volume":"36","author":"T Li","year":"2015","unstructured":"Li T, Li Q, Li S, Nie Y, Qiu L. Changes of angiopoietin 1 expression in G-CSF induced hematopoietic stem progenitor cells mobilization. Zhonghua Xue Ye Xue Za Zhi. 2015;36(5):418\u201321.","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"1658_CR26","first-page":"8485721","volume":"2016","author":"X Liu","year":"2016","unstructured":"Liu X, Hu X, Cai W, Lu W, Zheng L. Effect of granulocyte-colony stimulating factor on endothelial cells and osteoblasts. Biomed Res Int. 2016;2016:8485721.","journal-title":"Biomed Res Int"},{"issue":"9","key":"1658_CR27","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.1182\/blood.V92.9.3465","volume":"92","author":"Y Takamatsu","year":"1998","unstructured":"Takamatsu Y, Simmons PJ, Moore RJ, et al. Osteoclast-mediated bone resorption is stimulated during short-term administration of granulocyte colony-stimulating factor but is not responsible for hematopoietic progenitor cell mobilization. Blood. 1998;92(9):3465\u201373.","journal-title":"Blood"},{"issue":"2","key":"1658_CR28","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.cell.2005.10.041","volume":"124","author":"Y Katayama","year":"2006","unstructured":"Katayama Y, Battista M, Kao WM, Hidalgo A, Peired AJ, Thomas SA, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006;124(2):407\u201321.","journal-title":"Cell"},{"issue":"8","key":"1658_CR29","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1016\/j.bbmt.2015.05.005","volume":"21","author":"S Li","year":"2015","unstructured":"Li S, Li T, Chen Y, Nie Y, Li C, Liu L, et al. Granulocyte colony-stimulating factor induces osteoblast inhibition by B lymphocytes and osteoclast activation by T lymphocytes during hematopoietic stem\/progenitor cell mobilization. Biol Blood Marrow Transplant. 2015;21(8):1384\u201391.","journal-title":"Biol Blood Marrow Transplant"},{"issue":"4","key":"1658_CR30","first-page":"277","volume":"5","author":"AB Turhan","year":"2018","unstructured":"Turhan AB, Binay C, Bor O, Simsek E. The effects of short-term use of granulocyte colony-stimulating factor on bone metabolism in child cancer patients. North Clin Istanb. 2018;5(4):277.","journal-title":"North Clin Istanb"},{"issue":"2","key":"1658_CR31","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.exphem.2014.10.012","volume":"43","author":"M Rao","year":"2015","unstructured":"Rao M, Supakorndej T, Schmidt AP, Link DC. Osteoclasts are dispensable for hematopoietic progenitor mobilization by granulocyte colony-stimulating factor in mice. Exp Hematol. 2015;43(2):110\u20134.","journal-title":"Exp Hematol"},{"issue":"5","key":"1658_CR32","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1002\/jcp.24246","volume":"228","author":"S Li","year":"2013","unstructured":"Li S, Zhai Q, Zou D, Meng H, Xie Z, Li C, et al. A pivotal role of bone remodeling in granulocyte colony stimulating factor induced hematopoietic stem\/progenitor cells mobilization. J Cell Physiol. 2013;228(5):1002\u20139.","journal-title":"J Cell Physiol"}],"container-title":["BMC Oral Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-021-01658-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12903-021-01658-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-021-01658-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T04:02:53Z","timestamp":1623470573000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcoralhealth.biomedcentral.com\/articles\/10.1186\/s12903-021-01658-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,12]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1658"],"URL":"https:\/\/doi.org\/10.1186\/s12903-021-01658-1","relation":{},"ISSN":["1472-6831"],"issn-type":[{"value":"1472-6831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,12]]},"assertion":[{"value":"17 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki. And the study was carried out in compliance with the ARRIVE guidelines 2.0. All experiments involving studies performed with animals were approved according to the Ethics Committee of the Affiliated Zhongshan Hospital of Dalian University (ethics approval number: 2019081503).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"299"}}