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Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration

Author

Listed:
  • Tom W. Andrew

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Lauren S. Koepke

    (Stanford University School of Medicine)

  • Yuting Wang

    (Stanford University School of Medicine
    Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)

  • Michael Lopez

    (Stanford University School of Medicine)

  • Holly Steininger

    (Stanford University School of Medicine)

  • Danielle Struck

    (Stanford University School of Medicine)

  • Tatiana Boyko

    (Stanford University School of Medicine)

  • Thomas H. Ambrosi

    (Stanford University School of Medicine)

  • Xinming Tong

    (Stanford University)

  • Yuxi Sun

    (University of Alabama at Birmingham
    Birmingham VA Medical Center)

  • Gunsagar S. Gulati

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Matthew P. Murphy

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Owen Marecic

    (Stanford University School of Medicine)

  • Ruth Tevlin

    (Stanford Hospital and Clinics)

  • Katharina Schallmoser

    (Paracelsus Medical University of Salzburg)

  • Dirk Strunk

    (Paracelsus Medical University of Salzburg
    Paracelsus Medical University of Salzburg)

  • Jun Seita

    (RIKEN)

  • Stuart B. Goodman

    (Stanford University)

  • Fan Yang

    (Stanford University
    Stanford University)

  • Michael T. Longaker

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • George P. Yang

    (University of Alabama at Birmingham
    Birmingham VA Medical Center)

  • Charles K. F. Chan

    (Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

Sexually dimorphic tissues are formed by cells that are regulated by sex hormones. While a number of systemic hormones and transcription factors are known to regulate proliferation and differentiation of osteoblasts and osteoclasts, the mechanisms that determine sexually dimorphic differences in bone regeneration are unclear. To explore how sex hormones regulate bone regeneration, we compared bone fracture repair between adult male and female mice. We found that skeletal stem cell (SSC) mediated regeneration in female mice is dependent on estrogen signaling but SSCs from male mice do not exhibit similar estrogen responsiveness. Mechanistically, we found that estrogen acts directly on the SSC lineage in mice and humans by up-regulating multiple skeletogenic pathways and is necessary for the stem cell’s ability to self- renew and differentiate. Our results also suggest a clinically applicable strategy to accelerate bone healing using localized estrogen hormone therapy.

Suggested Citation

  • Tom W. Andrew & Lauren S. Koepke & Yuting Wang & Michael Lopez & Holly Steininger & Danielle Struck & Tatiana Boyko & Thomas H. Ambrosi & Xinming Tong & Yuxi Sun & Gunsagar S. Gulati & Matthew P. Murp, 2022. "Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34063-5
    DOI: 10.1038/s41467-022-34063-5
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    References listed on IDEAS

    as
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