{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T18:15:40Z","timestamp":1779387340189,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,19]]},"group-title":"Immunology","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"ADA Forsyth Pilot Grants","award":["AFIPLT01"],"award-info":[{"award-number":["AFIPLT01"]}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R90DE027638"],"award-info":[{"award-number":["R90DE027638"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["RF1AG062496"],"award-info":[{"award-number":["RF1AG062496"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004410","name":"TUBITAK","doi-asserted-by":"crossref","award":["2214\/A; 2219"],"award-info":[{"award-number":["2214\/A; 2219"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>The study investigated the interaction between estrogen deprivation and periodontitis, systemically, in the bone marrow, and locally in periodontal tissues using a mouse model.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We used the ligature-induced periodontitis (LIP) model concurrently with ovariectomy-induced estrogen deprivation. Bone marrow was assessed for myeloid cell proportion by flow cytometry. The femur metaphysis was examined histologically and by micro-CT. Cytokine responses of CD11b\n                    <jats:sup>+<\/jats:sup>\n                    myeloid cells to lipopolysaccharide stimulation were investigated\n                    <jats:italic>ex vivo<\/jats:italic>\n                    across ovary-intact (Sham), ovariectomized (OVX), and estrogen-replaced (OVX+E2) mice with or without periodontitis. Estrogen-related alterations in periodontitis, including microbiome composition and transcriptomic changes in the gingiva and dentoalveolar complex, were investigated by 16S rRNA sequencing and bulk RNA sequencing, respectively.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Ovariectomy increased osteoblast-like and adipocyte-like cell numbers in femoral marrow, whereas LIP reduced both populations (p = 0.020 and p = 0.029, respectively). LIP increased the bone marrow CD45\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic fraction in Sham mice. LPS-stimulated bone marrow CD11b\n                    <jats:sup>+<\/jats:sup>\n                    cells from OVX mice showed lower\n                    <jats:italic>Tnf\u03b1, Ccl2<\/jats:italic>\n                    , and\n                    <jats:italic>Il10<\/jats:italic>\n                    expression than Sham mice (p = 0.003, p = 0.005, and p = 0.001, respectively). OVX exacerbated LIP-associated alveolar bone loss, reducing BV\/TV (p = 0.003) and increasing osteoclast numbers (p = 0.012). Neither OVX nor E2 replacement significantly altered ligature-associated microbial composition in 16S rRNA sequencing. Bulk RNA sequencing demonstrated estrogen-responsive transcriptomic changes in both the gingiva and dentoalveolar complex, including OVX-associated gene-expression changes that returned toward Sham levels in OVX+E2 mice. These included genes related to stromal regulation (\n                    <jats:italic>Acan, Igfbp3, Erbb3<\/jats:italic>\n                    ) and immunity (\n                    <jats:italic>Gp2, Spib, B2m<\/jats:italic>\n                    ).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Periodontitis and estrogen deprivation exert combined effects on the bone marrow niche. Estrogen deprivation modulates immune- and healing-related gene expression in the gingiva and remaining dentoalveolar tissues during periodontitis.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.15.725533","type":"posted-content","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:10:32Z","timestamp":1779214232000},"source":"Crossref","is-referenced-by-count":0,"title":["Estrogen Deprivation and Periodontitis Interact Across Multiple Tissues"],"prefix":"10.64898","author":[{"given":"Nil","family":"Yakar","sequence":"first","affiliation":[{"name":"ADA Forsyth Institute, Somerville, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Hasturk","sequence":"additional","affiliation":[{"name":"ADA Forsyth Institute, Somerville, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Alvarez","family":"Rivas","sequence":"additional","affiliation":[{"name":"University at Buffalo School of Dental Medicine, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phrao","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"ADA Forsyth Institute, Somerville, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeliha","family":"Guney","sequence":"additional","affiliation":[{"name":"ADA Forsyth Institute, Somerville, MA"},{"name":"Medipol University Faculty of Dentistry, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birtan Tolga","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Harvard School of Dental Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Uzun","sequence":"additional","affiliation":[{"name":"PennState Cancer Institute, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Trackman","sequence":"additional","affiliation":[{"name":"ADA Forsyth Institute, Somerville, MA"},{"name":"Boston University Henry M. 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