{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:33:44Z","timestamp":1787762024336,"version":"build-2784847793"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Oral Implants Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Notch signaling pathway, known to influence bone resorption in several oral diseases, has not been analyzed in peri\u2010implantitis yet. Therefore, the aims of the present study were to determine the levels of Notch cascade, bone remodeling mediators, and pro\u2010inflammatory cytokines, in conjunction with clinical parameters, in subjects with peri\u2010implant mucositis and peri\u2010implantitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Clinical parameters: peri\u2010implant probing depth, bleeding on probing, suppuration on probing, and plaque index (PI) were recorded. Samples were collected from 130 participants, divided into peri\u2010implantitis (PI), peri\u2010implant mucositis (PM), and healthy implants (HI) group. Relative expression levels (REL) of Notch 1, Notch 2, Jagged 1, Hes 1, Hey 1, TNF\u2010\u03b1, IL\u201017, IL\u20101\u03b2, IL\u20106, RANKL, and OPG mRNA were determined by reverse transcriptase\u2010real\u2010time polymerase chain reaction. Quantitation of Notch 1, Il\u201017, and IL\u20106 proteins was performed using ELISA assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All clinical parameters were significantly higher in PI compared to HI. Significant decrease of Notch 1, and higher REL of Hey 1, IL\u20101\u03b2, IL\u20106, and RANKL were found in PI compared to HI. PM showed significant increase of IL\u20101\u03b2 REL in comparison with HI. In PI versus PM, significantly higher REL was found for Hey 1, TNF\u2010\u03b1, IL\u201017, IL\u20101\u03b2, IL\u20106, and RANKL. Additionally, higher protein concentrations of IL\u20106 and IL\u201017 were detected in PI versus PM and versus HI group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combined effect of Notch 1 down\u2010regulation and elevated expression of some key inflammation modulators might result in osteoclast activity increase and subsequent osteolysis in peri\u2010implantitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/clr.13850","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T15:36:30Z","timestamp":1632238590000},"page":"1496-1505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Notch down\u2010regulation and inflammatory cytokines and RANKL overexpression involvement in peri\u2010implant mucositis and peri\u2010implantitis: A cross\u2010sectional study"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-7848","authenticated-orcid":false,"given":"Iva","family":"Milinkovic","sequence":"first","affiliation":[{"name":"Department of Periodontology and Oral Medicine School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-0529","authenticated-orcid":false,"given":"Ana","family":"Djinic Krasavcevic","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Medicine School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8513-9313","authenticated-orcid":false,"given":"Nadja","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Department of Human Genetics School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0390-8789","authenticated-orcid":false,"given":"Zoran","family":"Aleksic","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Medicine School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-7589","authenticated-orcid":false,"given":"Jelena","family":"Carkic","sequence":"additional","affiliation":[{"name":"Department of Human Genetics School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Jezdic","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Medicine School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Jankovic","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Oral Medicine School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-7210","authenticated-orcid":false,"given":"Jelena","family":"Milasin","sequence":"additional","affiliation":[{"name":"Department of Human Genetics School of Dental Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12598"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.16\u20100424"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.11607\/jomi.2654"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707000200"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.17\u20100739"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12154"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010018\u20104694\u20103"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514551754"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12935"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2012.09.004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.118.2.503"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12801"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12354"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.080287"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010051X.2010.01537.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cid.12694"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100757.2010.00348.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12953"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/181849"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.11607\/prd.00.0679"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.045"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jper.18\u20100755"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910408300216"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.20\u20100159"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1708\u20108208.2006.00012.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3379"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2018.10.015"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412891200"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1708\u20108208.2007.00076.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jper.17\u20100721"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.13152"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/clr.13700"},{"key":"e_1_2_10_34_1","first-page":"116","article-title":"Diagnostic parameters for monitoring peri\u2010implant conditions","volume":"19","author":"Salvi G. E.","year":"2004","journal-title":"International Journal of Oral & Maxillofacial Implants"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061775"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jper.16\u20100350"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2016.08.021"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.01.006"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12201"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2005.76.11\u2010S.2033"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1563\/aaid\u2010joi\u2010D\u201016\u201000122"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2016.1140152"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2016\u20101002"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2354"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914\u2010017\u20100358\u2010z"}],"container-title":["Clinical Oral Implants Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/clr.13850","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/clr.13850","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/clr.13850","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T22:30:56Z","timestamp":1693002656000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/clr.13850"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":44,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1111\/clr.13850"],"URL":"https:\/\/doi.org\/10.1111\/clr.13850","archive":["Portico"],"relation":{},"ISSN":["0905-7161","1600-0501"],"issn-type":[{"value":"0905-7161","type":"print"},{"value":"1600-0501","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]},"assertion":[{"value":"2021-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}