Andrew Tom W, Koepke Lauren S, Wang Yuting, Lopez Michael, Steininger Holly, Struck Danielle, Boyko Tatiana, Ambrosi Thomas H, Tong Xinming, Sun Yuxi, Gulati Gunsagar S, Murphy Matthew P, Marecic Owen, Tevlin Ruth, Schallmoser Katharina, Strunk Dirk, Seita Jun, Goodman Stuart B, Yang Fan, Longaker Michael T, Yang George P, Chan Charles K F
Department of Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Nat Commun. 2022 Oct 30;13(1):6491. doi: 10.1038/s41467-022-34063-5.
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.
性二态组织由受性激素调节的细胞形成。虽然已知多种全身性激素和转录因子可调节成骨细胞和破骨细胞的增殖与分化，但决定骨再生中性别差异的机制尚不清楚。为了探究性激素如何调节骨再生，我们比较了成年雄性和雌性小鼠的骨折修复情况。我们发现雌性小鼠中骨骼干细胞（SSC）介导的再生依赖于雌激素信号传导，但雄性小鼠的SSC不表现出类似的雌激素反应性。从机制上讲，我们发现雌激素通过上调多种骨骼生成途径直接作用于小鼠和人类的SSC谱系，并且对于干细胞的自我更新和分化能力是必需的。我们的结果还提出了一种使用局部雌激素激素疗法加速骨愈合的临床适用策略。
