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Forschungsdatenbank PMU-SQQUID

Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration.
Andrew, TW; Koepke, LS; Wang, Y; Lopez, M; Steininger, H; Struck, D; Boyko, T; Ambrosi, TH; Tong, X; Sun, Y; Gulati, GS; Murphy, MP; Marecic, O; Telvin, R; Schallmoser, K; Strunk, D; Seita, J; Goodman, SB; Yang, F; Longaker, MT; Yang, GP; Chan, CKF;
Nat Commun. 2022; 13(1): 6491
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Schallmoser Katharina
Strunk Dirk

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 cells ability to self- renew and differentiate. Our results also suggest a clinically applicable strategy to accelerate bone healing using localized estrogen hormone therapy.


Useful keywords (using NLM MeSH Indexing)

Humans

Male

Female

Mice

Animals

Osteoblasts*/metabolism

Stem Cells*

Cell Differentiation

Osteoclasts

Estrogens/pharmacology

Estrogens/metabolism