Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration

This study investigates the role of sex hormones, specifically estrogen, in bone regeneration. It compares bone fracture repair between male and female mice and analyzes human skeletal stem cells. The research uncovers that estrogen signaling is critical for skeletal stem cell-mediated bone regeneration in females, but not in males. The study found that estrogen directly influences skeletal stem cells, promoting their ability to self-renew and differentiate into bone-forming cells. This effect is more pronounced in females. The deficiency in skeletal stem cell activity caused by estrogen loss (as seen after menopause) can be reversed by localized estrogen treatment. The research suggests a new clinical approach using localized estrogen therapy to accelerate bone healing, particularly beneficial for women experiencing impaired bone regeneration due to estrogen deficiency. This method aims to bypass the risks associated with systemic estrogen exposure.

• 1
  Skeletal regeneration is sexually dimorphic: female mice require estrogen for skeletal stem cell-mediated bone regeneration, while male mice do not exhibit similar estrogen responsiveness.
• 2
  Estrogen directly acts on skeletal stem cells (SSCs) to up-regulate skeletogenic pathways, promoting self-renewal and differentiation into bone-forming cells.
• 3
  Localized estrogen hormone therapy can reverse SSC deficiency and bone loss following ovariectomy and aging, suggesting a potential clinical strategy to accelerate bone healing.