{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:25:45Z","timestamp":1773293145382,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,6,20]],"date-time":"2014-06-20T00:00:00Z","timestamp":1403222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Government of Malaysia"},{"name":"New Zealand Dental Association Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Modeling of periodontal bone regeneration in a large animal enables better examination of the spatial and temporal regulation of osteogenesis and the remodeling of the healing defect. <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> RANKL<\/jats:styled-content> and osteoprotegerin (<jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content>) are known to be important regulators of bone healing. The aim of this study was to create periodontal defects surgically in a large animal model and to examine bone regeneration and the expression of <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> RANKL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content> proteins in the defect site during bone regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>Periodontal defects were made in the furcation of the second mandibular premolar of sheep. Wound healing was examined 6\u00a0h, and 1, 4 and 6\u00a0wk after surgery and in control tissue. The teeth and defect region were decalcified and paraffin embedded. Immunohistochemistry for <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> RANKL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content> was conducted. Osteoclasts were identified using TRAP staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The defects were examined at different time points after surgery and by 6\u00a0wk the defect region had fully regenerated with new bone, albeit less dense than that in the unwounded controls. <jats:styled-content style=\"fixed-case\">RANK\u2010<\/jats:styled-content>positive osteoclasts were present at the edge of the wound from week 1 and were found within the defect at week 6, corresponding to osteoclast activation and bone remodeling. <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content> staining increased from week 1 compared with unwounded tissue, and peaked at 4 and 6\u00a0wk, as the osteoblast numbers increased. At the same time, <jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content> immunostaining was high in controls and at week 6, suggesting that it may act to block <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content> and control the bone remodeling within the defect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Distinctive temporal and spatial expression patterns for <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> RANKL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content> proteins were observed during healing of surgically created periodontal wounds in a sheep model. The research identifies possible therapeutic approaches to periodontal bone repair via modulation of these members of the tumor necrosis factor family.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12196","type":"journal-article","created":{"date-parts":[[2014,6,20]],"date-time":"2014-06-20T11:49:45Z","timestamp":1403264985000},"page":"211-219","source":"Crossref","is-referenced-by-count":18,"title":["Localization of RANK, RANKL and osteoprotegerin during healing of surgically created periodontal defects in sheep"],"prefix":"10.1111","volume":"50","author":[{"given":"N. A.","family":"Baharuddin","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Oral Medicine and Periodontology University of Malaya Kuala Lumpur Malaya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. E.","family":"Coates","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Sir John Walsh Research Institute University of Otago Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Cullinan","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Sir John Walsh Research Institute University of Otago Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Seymour","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Sir John Walsh Research Institute University of Otago Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Sir John Walsh Research Institute University of Otago Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,6,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2005.03.002"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02441211"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/BF02406132","article-title":"The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone","volume":"36","author":"Parfitt AM","year":"1984","journal-title":"Calcif Tissue Int"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240550303"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.1.2"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3597"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.20.3.0367"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2003.10.005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80209-3"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1210\/endo.139.3.5837","article-title":"Identity of osteoclatogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG) \u2013 a mechanism by which OPG\/ OCIF inhibits osteoclastogenesis in vitro","volume":"139","author":"Yasuda H","year":"1998","journal-title":"Endocrinology"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/16852"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8697"},{"key":"e_1_2_6_16_1","volume-title":"Suspected Periodontopathic Bacteria in Man and in Sheep","author":"Frisken KW","year":"1987"},{"key":"e_1_2_6_17_1","volume-title":"A Transmission Electron Microscope Study Comparing the Ultrastructure of Collagen in the Upper Dental Pad of Periodontally Diseased and Healthy Sheep","author":"Duncan WJ","year":"1992"},{"key":"e_1_2_6_18_1","first-page":"753","article-title":"A new animal model for guided tissue regeneration","volume":"74","author":"Danesh\u2010Meyer MJ","year":"1995","journal-title":"J Periodont Res"},{"key":"e_1_2_6_19_1","first-page":"65","volume-title":"Healing in Class 2 Furcation Defects in A Sheep using Plaster of Paris Alone and in Conjunction with Autogenous Bone","author":"Cole N","year":"1999"},{"key":"e_1_2_6_20_1","volume-title":"Transforming Growth Factor Beta One in GTR in Sheep","author":"Mohammed S","year":"1997"},{"key":"e_1_2_6_21_1","volume-title":"Periodontal Guided Tissue Regeneration in Sheep using Cardiovascular Patch or Gore\u2010Tex Periodontal Material and Resorbable Hydroxyapatite","author":"Whelan JRK","year":"1996"},{"key":"e_1_2_6_22_1","first-page":"235","volume-title":"Animal Physiology: Adaptation and Environment","author":"Schmidt\u2010Nielson K","year":"1975"},{"issue":"4","key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"277S","DOI":"10.1016\/8756-3282(95)00026-A","article-title":"The potential of sheep for the study of osteopenia: current status and comparison with other animal models","volume":"16","author":"Newman E","year":"1995","journal-title":"Bone"},{"key":"e_1_2_6_24_1","volume-title":"Animal Models in Orthopaedic Research","author":"An Y","year":"1999"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-2-24"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2009.00793.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63560-2"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6603"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00121-0"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10763"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/46303"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-002-8530-7"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.F.00409"},{"key":"e_1_2_6_34_1","first-page":"783","article-title":"Osteoprotegerin prevents and reverses hypercalcaemia in a murine model of humoral hypercalcaemia of malignancy","volume":"60","author":"Capparelli C","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.2.348"}],"container-title":["Journal of Periodontal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjre.12196","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjre.12196","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.12196","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T15:46:17Z","timestamp":1696175177000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jre.12196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,20]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["10.1111\/jre.12196"],"URL":"https:\/\/doi.org\/10.1111\/jre.12196","archive":["Portico"],"relation":{},"ISSN":["0022-3484","1600-0765"],"issn-type":[{"value":"0022-3484","type":"print"},{"value":"1600-0765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,20]]}}}