Inflammation is essential for skeletal muscle repair following acute injury, and successful muscle regeneration requires a balance between pro- and anti-inflammatory signaling. Estrogen regulates inflammatory responses, suggesting a role in tissue repair. CD169+ macrophages are also associated with tissue repair. However, these cells and related interferon-inducible genes have not been investigated in regenerating muscle.To examine how 17β-estradiol treatment influences the expression and co-expression network of Siglec1 (encoding CD169), an interferon-inducible gene, during muscle regeneration.Ovariectomized mice received either 17β-estradiol or placebo before undergoing a standardized crush injury to hindlimb muscle groups and exposure to simulated flight. Mice were euthanized at 32-h, 96-h, or 192-h postinjury. Differential gene expression analysis was performed on injured muscles to assess treatment-related transcriptional changes, and additional muscles were evaluated for regeneration stage and CD169 protein expression.At 192-h postinjury, Siglec1 was among the top upregulated genes in 17β-estradiol-treated mice relative to placebo mice, which reflected a decline in Siglec1 expression over time in the placebo group. Correlation analysis revealed that Siglec1 was strongly associated with interferon-related genes under placebo treatment, whereas the connectivity of Siglec1 under 17β-estradiol treatment was weakened. Immunohistochemistry confirmed stronger CD169 staining in regenerating muscle of 17β-estradiol-treated mice.Siglec1 expression is more stable in an estrogen state compared to an ovarian-hormone-deficient state. Understanding how estrogen deficiency alters inflammatory signaling after muscle injury may inform interventions to promote recovery in postmenopausal women, who may be at risk for impaired muscle repair. Background: Objective: Methods: Results: Conclusion:
