{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:48:57Z","timestamp":1791622137694,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701013"],"award-info":[{"award-number":["81701013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271011"],"award-info":[{"award-number":["82271011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018806","name":"Department of Science and Technology of Hubei Province","doi-asserted-by":"publisher","award":["2020CFB690"],"award-info":[{"award-number":["2020CFB690"]}],"id":[{"id":"10.13039\/501100018806","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthod Craniofacial Res"],"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n Orthodontically induced root resorption involves the destruction of cementum, and in severe cases, dentine. Cementoblasts are cells responsible for depositing and mineralizing cementum, and they can also communicate with osteoclasts to indirectly regulate cementum destruction. This study aimed to elucidate the impact of TNF\u2010\u03b1 on IL\u20106 and M\u2010CSF, two potent osteoclast\u2010activating cytokines secreted by cementoblasts. Additionally, the study explored the combined effects of BMP\u20102, BMP\u20104, BMP\u20106, BMP\u20107 and TNF\u2010\u03b1.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n We utilized the immortalized mouse cementoblast cell line OCCM\u201030. Cells were incubated with TNF\u2010\u03b1, followed by RT\u2010qPCR and ELISA to assess IL\u20106 and M\u2010CSF expression. Prior to TNF\u2010\u03b1 stimulation, cells were pre\u2010incubated with inhibitors targeting p38 MAPK, Erk1\/2, JNK, PI3K\u2010Akt, or NF\u2010\u03baB pathways, and IL\u20106 and M\u2010CSF levels were analysed by RT\u2010qPCR. Cells were also treated with combinations of BMP\u20102, BMP\u20104, BMP\u20106, BMP\u20107 and TNF\u2010\u03b1, and their synergistic effects on IL\u20106 and M\u2010CSF were evaluated by RT\u2010qPCR and ELISA.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n TNF\u2010\u03b1 significantly increased both IL\u20106 and M\u2010CSF mRNA levels, as well as their secreted levels. Blocking the NF\u2010\u03baB pathway partially reversed TNF\u2010\u03b1\u2010induced upregulation of IL\u20106 and M\u2010CSF. BMP\u20104 and BMP\u20102 further potentiated TNF\u2010\u03b1\u2010induced upregulation of IL\u20106 and M\u2010CSF, while BMP\u20106 and BMP\u20107 had no effect.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n TNF\u2010\u03b1 increased IL\u20106 and M\u2010CSF expression in cementoblasts via the NF\u2010\u03baB pathway. BMP\u20104 and BMP\u20102 exacerbated the TNF\u2010\u03b1\u2010induced effect on IL\u20106 and M\u2010CSF.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ocr.70193","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:09:43Z","timestamp":1791619783000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulatory Effects of Bone Morphogenetic Protein\u20104 on Tumour Necrosis Factor\u2010Alpha\u2010Induced IL\u20106 and M\u2010CSF Expression in Cementoblasts"],"prefix":"10.1111","author":[{"given":"Yunlong","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Department of Orthodontics, School & Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Dentofacial Deformities in Children, School & Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4261-9034","authenticated-orcid":false,"given":"Zhengguo","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Department of Periodontology, School & Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-0015","authenticated-orcid":false,"given":"Hong","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Department of Orthodontics, School & Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Dentofacial Deformities in Children, School & Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9981-7982","authenticated-orcid":false,"given":"Zhijian","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Department of Orthodontics, School & Hospital of Stomatology Wuhan University Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Dentofacial Deformities in Children, School & Hospital of Stomatology Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"161","article-title":"Hyalinization and Root Resorption During Early Orthodontic Tooth Movement in Adolescents","volume":"68","author":"Kurol J.","year":"1998","journal-title":"Angle Orthodontist"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0889-5406(96)70160-9","article-title":"Prevalence and Severity of Apical Root Resorption and Alveolar Bone Loss in Orthodontically Treated Adults","volume":"109","author":"Lupi J. E.","year":"1996","journal-title":"American Journal of Orthodontics and Dentofacial Orthopedics"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2319\/032112-240.1","article-title":"Apical Root Resorption due to Orthodontic Treatment Detected by Cone Beam Computed Tomography","volume":"83","author":"Castro I. O.","year":"2013","journal-title":"Angle Orthodontist"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1177\/154405910708601011","article-title":"PGE2 Activates Cementoclastogenesis by Cementoblasts via EP4","volume":"86","author":"Oka H.","year":"2007","journal-title":"Journal of Dental Research"},{"key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1902\/jop.2007.060257","article-title":"Cyclooxygenase\u20102\u2010Dependent Prostaglandin E(2) Upregulates Interleukin (IL)\u20101alpha\u2010Induced IL\u20106 Generation in Mouse Cementoblasts","volume":"78","author":"Noguchi K.","year":"2007","journal-title":"Journal of Periodontology"},{"key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1093\/ejo\/cjac010","article-title":"Effect of Irisin on the Expression of Osteoclast\u2010Related Genes in Cementoblasts","volume":"44","author":"Zhao C.","year":"2022","journal-title":"European Journal of Orthodontics"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","DOI":"10.4110\/in.2018.18.e8","article-title":"Regulation of Osteoclast Differentiation by Cytokine Networks","volume":"18","author":"Amarasekara D. 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P.","year":"2007","journal-title":"European Journal of Oral Sciences"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1177\/0022034515590349","article-title":"Effects of TNF\u2010Alpha on Cementoblast Differentiation, Mineralization, and Apoptosis","volume":"94","author":"Wang Y. L.","year":"2015","journal-title":"Journal of Dental Research"},{"key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S8756-3282(99)00096-4","article-title":"Immortalized Cementoblasts and Periodontal Ligament Cells in Culture","volume":"25","author":"D'Errico J. 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A.","year":"1988","journal-title":"Journal of Dental Research"},{"key":"e_1_2_13_19_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.bone.2004.04.023","article-title":"Lipopolysaccharide Stimulates Expression of Osteoprotegerin and Receptor Activator of NF\u2010Kappa B Ligand in Periodontal Ligament Fibroblasts Through the Induction of Interleukin\u20101 Beta and Tumor Necrosis Factor\u2010Alpha","volume":"35","author":"Wada N.","year":"2004","journal-title":"Bone"},{"key":"e_1_2_13_20_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00011-010-0253-x","article-title":"Effects of HSP70 on the Compression Force\u2010Induced TNF\u2010Alpha and RANKL Expression in Human Periodontal Ligament Cells","volume":"60","author":"Mitsuhashi M.","year":"2011","journal-title":"Inflammation Research"},{"key":"e_1_2_13_21_1","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1359\/jbmr.1998.13.8.1290","article-title":"TNF\u2010Alpha Increases Expression of IL\u20106 and ICAM\u20101 Genes Through Activation of NF\u2010kappaB in Osteoblast\u2010Like ROS17\/2.8 Cells","volume":"13","author":"Kurokouchi K.","year":"1998","journal-title":"Journal of Bone and Mineral Research"},{"key":"e_1_2_13_22_1","doi-asserted-by":"crossref","first-page":"F571","DOI":"10.1152\/ajprenal.00113.2014","article-title":"Rho\u2010Kinase Regulation of TNF\u2010\u03b1\u2010Induced Nuclear Translocation of NF\u2010\u03baB RelA\/p65 and M\u2010CSF Expression via p38 MAPK in Mesangial Cells","volume":"307","author":"Matoba K.","year":"2014","journal-title":"American Journal of Physiology. Renal Physiology"},{"key":"e_1_2_13_23_1","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.bbrc.2007.03.099","article-title":"TNF\u2010Alpha Inhibits BMP\u2010Induced Osteoblast Differentiation Through Activating SAPK\/JNK Signaling","volume":"356","author":"Mukai T.","year":"2007","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"e_1_2_13_24_1","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S8756-3282(00)00358-6","article-title":"Direct Stimulation of Osteoclastic Bone Resorption by Bone Morphogenetic Protein (BMP)\u20102 and Expression of BMP Receptors in Mature Osteoclasts","volume":"27","author":"Kaneko H.","year":"2000","journal-title":"Bone"},{"key":"e_1_2_13_25_1","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1210\/endo.142.8.8300","article-title":"Bone Morphogenetic Protein 2 Stimulates Osteoclast Differentiation and Survival Supported by Receptor Activator of Nuclear Factor\u2010kappaB Ligand","volume":"142","author":"Itoh K.","year":"2001","journal-title":"Endocrinology"},{"key":"e_1_2_13_26_1","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/jcb.22462","article-title":"Bone Morphogenic Protein 2 Directly Enhances Differentiation of Murine Osteoclast Precursors","volume":"109","author":"Jensen E. D.","year":"2010","journal-title":"Journal of Cellular Biochemistry"},{"key":"e_1_2_13_27_1","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1359\/jbmr.060411","article-title":"Bone Morphogenetic Proteins in Bone Stimulate Osteoclasts and Osteoblasts During Bone Development","volume":"21","author":"Okamoto M.","year":"2006","journal-title":"Journal of Bone and Mineral Research"},{"key":"e_1_2_13_28_1","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1177\/154405910508400501","article-title":"Are Cementoblasts a Subpopulation of Osteoblasts or a Unique Phenotype?","volume":"84","author":"Bosshardt D. D.","year":"2005","journal-title":"Journal of Dental Research"}],"container-title":["Orthodontics & Craniofacial Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ocr.70193","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ocr.70193","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ocr.70193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T08:09:47Z","timestamp":1791619787000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ocr.70193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,10]]},"references-count":27,"alternative-id":["10.1111\/ocr.70193"],"URL":"https:\/\/doi.org\/10.1111\/ocr.70193","archive":["Portico"],"relation":{},"ISSN":["1601-6335","1601-6343"],"issn-type":[{"value":"1601-6335","type":"print"},{"value":"1601-6343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,10]]},"assertion":[{"value":"2026-04-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ocr.70193"}}