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Here, we first demonstrated by cell lineage tracing and mineral double\u2010labeling approaches that murine PDL progenitor cells display a 2\u2010 and 3\u2010fold higher mineral deposition rate than the periosteum and endosteum at the age of 4 weeks, respectively. We next proved that the pathologic changes in osteocytes (Ocys; changes from a spindle shape to round shape with a &gt;50% reduction in the dendrite number\/length, and an increase in SOST) are the key pathologic factors responsible for bone and PDL damage in periostin\u2010null mice (a periodontitis animal model) using a newly developed 3\u2010dimensional FITC\u2010Imaris technique. Importantly, we proved that deleting the\n                    <jats:italic>Sost<\/jats:italic>\n                    gene (a potent inhibitor of WNT signaling) or blocking sclerostin function by using the mAb in this periodontitis model significantly restores bone and PDL defects (\n                    <jats:italic>n<\/jats:italic>\n                    = 4\u20105;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). Together, identification of the key contribution of the PDL in normal alveolar bone formation, the pathologic changes of the Ocys in periodontitis bone loss, and the novel link between sclerostin and Wnt signaling in the PDL will aid future drug development in the treatment of patients with periodontitis.\u2014Ren, Y., Han, X., Ho, S. P., Harris, S. E., Cao, Z., Economides, A. N., Qin, C., Ke, H., Liu, M., Feng, J. Q. Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 29, 2702\u20102711 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-265496","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T22:52:23Z","timestamp":1426027943000},"page":"2702-2711","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Removal of SOST or blocking its product sclerostin rescues defects in the periodontitis mouse model"],"prefix":"10.1096","volume":"29","author":[{"given":"Yinshi","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Texas A&amp;M University Baylor College of Dentistry Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Texas A&amp;M University Baylor College of Dentistry Dallas Texas USA"},{"name":"State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita P.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Preventive and Restorative Dental Sciences University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen E.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Periodontics University of Texas Health Science Center, San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengguo","family":"Cao","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology &amp; Key Laboratory of Oral Biomedicine, School &amp; Hospital of Stomatology, Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris N.","family":"Economides","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Texas A&amp;M University Baylor College of Dentistry Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huazhu","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Metabolic Disorders Amgen Incorporated Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Metabolic Disorders Amgen Incorporated Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Q.","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Texas A&amp;M University Baylor College of Dentistry Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67728-8"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1994.65.7.676"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/08959374930070010301"},{"key":"e_1_2_7_5_1","first-page":"5","article-title":"New considerations in the prevalence of periodontal disease","volume":"2","author":"Fox C. 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