bioRxiv : the preprint server for biology · 2026
Estrogen Deprivation and Periodontitis Interact Across Multiple Tissues.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Yakar Nil, Hasturk Hatice, Rivas Carla Alvarez, Zimmerman Phrao, Guney Zeliha, Yilmaz Birtan Tolga, Uzun Yasin, Trackman Philip, Kantarci Alpdogan
Аннотация
UNLABELLED: The study investigated the interaction between estrogen deprivation and periodontitis, systemically, in the bone marrow, and locally in periodontal tissues using a mouse model.
METHODS: 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+ myeloid cells to lipopolysaccharide stimulation were investigated ex vivo 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.
RESULTS: 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+ hematopoietic fraction in Sham mice. LPS-stimulated bone marrow CD11b+ cells from OVX mice showed lower Tnfα, Ccl2, and Il10 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 (Acan, Igfbp3, Erbb3) and immunity (Gp2, Spib, B2m).
CONCLUSION: 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.
METHODS: 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+ myeloid cells to lipopolysaccharide stimulation were investigated ex vivo 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.
RESULTS: 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+ hematopoietic fraction in Sham mice. LPS-stimulated bone marrow CD11b+ cells from OVX mice showed lower Tnfα, Ccl2, and Il10 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 (Acan, Igfbp3, Erbb3) and immunity (Gp2, Spib, B2m).
CONCLUSION: 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.