{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:54:30Z","timestamp":1791888870973,"version":"4.3.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T00:00:00Z","timestamp":1369353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, is a key physiological inhibitor of osteogenesis. Pharmacologic inhibition of sclerostin using sclerostin-neutralizing monoclonal antibody (Scl-Ab) thus increases bone formation, bone mass and bone strength in models of osteopenia and fracture repair. This study assessed the therapeutic potential of Scl-Ab to stimulate alveolar bone regeneration following experimental periodontitis (EP). Ligature-induced EP was induced in rats to generate localized alveolar bone defects. Following 4 weeks of disease induction, Scl-Ab (+EP) or vehicle (+\/\u2212 EP) were systemically delivered, twice weekly for up to 6 wks to determine the ability of Scl-Ab to regenerate bone around tooth-supporting osseous defects. 3 and 6 wks after the initiation of Scl-Ab or vehicle treatment, femur and maxillary jawbones were harvested for histology, histomorphometry, and micro-computed tomography (micro-CT) of linear alveolar bone loss (ABL) and volumetric measures of bone support, including bone volume fraction (BVF) and tissue mineral density (TMD). Serum was analyzed to examine bone turnover markers during disease and regenerative therapy. Vehicle\u2009+\u2009EP animals exhibited maxillary bone loss (BVF, TMD and ABL) at ligature removal and thereafter. 6 weeks of Scl-Ab significantly improved maxillary bone healing, as measured by BVF, TMD and ABL, when compared to vehicle\u2009+\u2009EP. After 6 weeks of treatment, BVF and TMD values in the Scl-Ab\u2009+\u2009EP group were similar to those of healthy controls. Serum analysis demonstrated higher levels of bone formation markers osteocalcin and PINP in Scl-Ab treatment groups. Scl-Ab restored alveolar bone mass following experimental periodontitis. These findings warrant further exploration of Scl-Ab therapy in this and other oral bone defect disease scenarios. \u00a9 2013 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.1984","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T12:24:30Z","timestamp":1369398270000},"page":"2347-2356","source":"Crossref","is-referenced-by-count":99,"title":["Sclerostin antibody stimulates bone regeneration after experimental periodontitis"],"prefix":"10.1093","volume":"28","author":[{"given":"Andrei D","family":"Taut","sequence":"first","affiliation":[{"name":"Department of Periodontics and Oral MedicineSchool of DentistryUniversity of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of CariologyRestorative Sciences, and Endodontics, School of Dentistry, University of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyuk","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of DentistryKyung Hee UniversitySeoulSouth Korea"},{"name":"Department of Periodontics and Oral MedicineSchool of DentistryUniversity of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Galindo-Moreno","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery and Implant DentistryUniversity of GranadaGranadaSpain"},{"name":"Department of Periodontics and Oral MedicineSchool of DentistryUniversity of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica S","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral MedicineSchool of DentistryUniversity of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James V","family":"Sugai","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral MedicineSchool of DentistryUniversity of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua Z","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Metabolic DisordersAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Metabolic DisordersAmgen Inc.Thousand OaksCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William V","family":"Giannobile","sequence":"additional","affiliation":[{"name":"Department of Biomedical EngineeringCollege of EngineeringUniversity of MichiganAnn ArborMIUSA"},{"name":"Department of Periodontics and Oral MedicineSchool of DentistryUniversity of MichiganAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,5,24]]},"reference":[{"issue":"9499","key":"2024020318343551200_jbmr1984-bib-0001","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","article-title":"Periodontal diseases","volume":"366","author":"Pihlstrom","year":"2005","journal-title":"Lancet."},{"key":"2024020318343551200_jbmr1984-bib-0002","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1902\/jop.2008.080174","article-title":"Host-response therapeutics for periodontal diseases","author":"Giannobile","year":"2008","journal-title":"J Periodontol."},{"key":"2024020318343551200_jbmr1984-bib-0003","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1196\/annals.1384.028","article-title":"Oral fluid-based biomarkers of alveolar bone loss in periodontitis","volume":"1098","author":"Kinney","year":"2007","journal-title":"Ann NY Acad Sci."},{"issue":"1","key":"2024020318343551200_jbmr1984-bib-0004","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1902\/annals.2003.8.1.266","article-title":"Guided tissue regeneration for the treatment of periodontal intrabony and furcation defects","volume":"8","author":"Murphy","year":"2003","journal-title":"A systematic review. Ann Periodontol."},{"issue":"5","key":"2024020318343551200_jbmr1984-bib-0005","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1210\/er.2011-1060","article-title":"Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases","volume":"33","author":"Ke","year":"2012","journal-title":"Endocr Rev."},{"issue":"29","key":"2024020318343551200_jbmr1984-bib-0006","doi-asserted-by":"crossref","first-page":"26770","DOI":"10.1074\/jbc.M504308200","article-title":"SOST is a ligand for LRP5\/LRP6 and a Wnt signaling inhibitor","volume":"280","author":"Semenov","year":"2005","journal-title":"J Biol Chem."},{"issue":"20","key":"2024020318343551200_jbmr1984-bib-0007","doi-asserted-by":"crossref","first-page":"19883","DOI":"10.1074\/jbc.M413274200","article-title":"Sclerostin binds to LRP5\/6 and antagonizes canonical Wnt signaling","volume":"280","author":"Li","year":"2005","journal-title":"J Biol 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