Sex-based differential regulation of bacterial-induced bone resorption

M. S. Valerio, D. S. Basilakos, J. E. Kirkpatrick, M. Chavez, J. Hathaway-Schrader, B. A. Herbert, K. L. Kirkwood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background and Objective: Periodontal disease pathogenesis is comprised of the complex inflammatory immune response to oral bacterial dysbiosis. Like other inflammatory diseases, there is sexual dimorphism evident in periodontal diseases. During periodontitis, inflammatory chemokines direct neutrophils to migrate to the site of infection to neutralize the pathogen. Interestingly, these same chemokines are also involved in regulating pathogen-induced osteoclast formation. Previous reports show differences in bone turnover and lymphocyte recruitment between sexes. We hypothesize that chemokine expression is differentially regulated by sex and thus results in differential osteoclast formation. Material and Methods: Male and female mice were utilized to isolate neutrophils based on expression of Ly6G-specific, as well as defined osteoclast progenitors. Cells were stimulated with lipopolysaccharide (LPS; 100 ng/mL) then analyzed for neutrophil infiltration and gene expression. Defined osteoclast progenitors were primed: macrophage-colony stimulating factor (25 ng/mL), receptor activator of NF-κB ligand (50 ng/mL), then stimulated with LPS. Osteoclasts were enumerated via TRAP stain and mRNA isolated for gene expression analysis via quantitative polymerase chain reaction. Results: In response to LPS, male neutrophils in vitro respond with increased chemokine expression and significantly more osteoclast formed in response to LPS compared to females. Conclusions: Findings support observations in humans regarding a sexual dimorphism in oral bacterial infections of alveolar bone loss. Males have a strong inflammatory response to bacterial infection, resulting in increased inflammatory microenvironment, reduced pathogenic bacteria clearance and increased osteoclast-driven bone loss in response to differential expression of key chemokines.

Original languageEnglish
Pages (from-to)377-387
Number of pages11
JournalJournal of Periodontal Research
Issue number3
StatePublished - Jun 2017
Externally publishedYes


  • chemokines
  • neutrophils
  • oral infections
  • osteoclastogenesis


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