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Updated: Jun 5, 2026
07:15
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Estrogen Deprivation and Periodontitis Interact Across Multiple Tissues
Nil Yakar1, Hatice Hasturk1, Carla Alvarez Rivas2
1ADA Forsyth Institute, Somerville, MA.
Biorxiv : the Preprint Server for Biology
|June 4, 2026
Summary
Estrogen deprivation worsens periodontitis-related bone loss and alters immune cell function. Estrogen replacement partially restores gene expression in affected tissues, highlighting its protective role.
Area of Science:
- Oral biology and immunology
- Endocrinology and bone metabolism
- Microbiome research
Background:
- Estrogen plays a crucial role in maintaining bone health and immune homeostasis.
- Periodontitis, a chronic inflammatory disease, affects periodontal tissues and can have systemic implications.
- The interplay between estrogen deficiency and periodontitis is not fully understood, particularly concerning bone marrow and local tissue responses.
Purpose of the Study:
- To investigate the combined effects of estrogen deprivation and ligature-induced periodontitis (LIP) on bone marrow and periodontal tissues.
- To analyze immune cell function and gene expression changes in response to these conditions.
- To evaluate the impact of estrogen replacement therapy on these alterations.
Main Methods:
- A mouse model combining ovariectomy-induced estrogen deprivation with LIP was employed.
- Bone marrow myeloid cell proportions were assessed via flow cytometry.
- Femur metaphysis was analyzed using histology and micro-CT.
- Ex vivo cytokine responses of myeloid cells to lipopolysaccharide (LPS) were measured.
- Microbiome composition and gingival/dentoalveolar transcriptomic changes were analyzed using 16S rRNA and bulk RNA sequencing, respectively.
Main Results:
- Ovariectomy increased osteoblast-like and adipocyte-like cells in bone marrow, while LIP decreased them.
- Estrogen deprivation exacerbated LIP-induced alveolar bone loss, increasing osteoclast numbers.
- Bone marrow myeloid cells from ovariectomized mice showed reduced expression of TNFα, CCL2, and IL10 upon LPS stimulation.
- Transcriptomic analysis revealed estrogen-responsive gene expression changes in gingival and dentoalveolar tissues during periodontitis.
Conclusions:
- Estrogen deprivation and periodontitis synergistically impact the bone marrow niche and exacerbate alveolar bone loss.
- Estrogen deficiency modulates immune cell function and alters the expression of key genes involved in immunity and tissue regulation in periodontal tissues.
- Estrogen replacement therapy may partially reverse these detrimental effects, underscoring estrogen's protective role in periodontitis.
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