Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration.
Sexually dimorphic estrogen sensing in skeletal stem cells controls skeletal regeneration.
复制标题
骨骼干细胞中的性二态雌激素传感控制骨骼再生。
DOI：
10.1038/s41467-022-34063-5
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发表时间：
2022-10-30
影响因子：
16.6
通讯作者：
Chan, Charles K. F.
中科院分区：
文献类型：
--
作者：
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;Telvin, Ruth;Schallmoser, Katharina;Strunk, Dirk;Seita, Jun;Goodman, Stuart B.;Yang, Fan;Longaker, Michael T.;Yang, George P.;Chan, Charles K. F.
性二型组织是由受性激素调节的细胞形成的。虽然已知许多系统激素和转录因子调节成骨细胞和破骨细胞的增殖和分化，但决定骨再生中性别二型差异的机制尚不清楚。为了探索性激素如何调节骨再生，我们比较了成年雄性和雌性小鼠之间的骨折修复。我们发现雌性小鼠的骨骼干细胞（SSC）介导的再生依赖于雌激素信号，但雄性小鼠的SSC没有表现出类似的雌激素反应。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中的SSC谱系，并且是干细胞自我更新和分化能力所必需的。我们的研究结果还表明，临床上适用的战略，以加速骨愈合局部雌激素治疗。骨骼相关的性二态性状是如何调节的，还没有在干细胞水平上进行过研究。在这里，作者表明，雌性而非雄性小鼠的骨骼干细胞（SSC）直接受雌激素信号的控制，这可以增强以改善骨折修复。
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. How bone-related sexually dimorphic traits are regulated hasn’t been examined at the stem cell level. Here the authors show that skeletal stem cells (SSC), in female but not male mice, are directly controlled by estrogen signaling, which could be augmented to improve fracture repair.
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影响因子：
82.9
作者：
Farr JN;Xu M;Weivoda MM;Monroe DG;Fraser DG;Onken JL;Negley BA;Sfeir JG;Ogrodnik MB;Hachfeld CM;LeBrasseur NK;Drake MT;Pignolo RJ;Pirtskhalava T;Tchkonia T;Oursler MJ;Kirkland JL;Khosla S
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Khosla S
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158.5
作者：
Cummings, SR;Browner, WS;Ettinger, B
通讯作者：
Ettinger, B
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168.9
作者：
Beral, V;Bull, D;Reeves, G
通讯作者：
Reeves, G
影响因子：
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作者：
Elmlinger, Martin W.;Kuehnel, Werner;Ranke, Michael B.
通讯作者：
Ranke, Michael B.
影响因子：
64.8
作者：
Galloway, Jenna L.;Delgado, Irene;Tabin, Clifford J.
通讯作者：
Tabin, Clifford J.