Targeting MCH Neuroendocrine Circuit in Lateral Hypothalamus to Protect Against Skeletal Senescence
Abstract: Neuroendocrine regulation is essential for maintaining metabolic homeostasis. However, whether neuroendocrine pathway influence bone metabolism and skeletal senescence is unelucidated. Here, a central neuroendocrine circuit is identified that directly controls osteogenesis. Using virus based tracing, this study is identified that melanin concentrating hormone (MCH) expressing neurons in the lateral hypothalamus (LH) are connected to the bone. Chemogenetic activation of MCH neurons in the LH induces osteogenesis, whereas inhibiting these neurons reduces osteogenesis. Meanwhile, MCH is released into the circulation upon chemogenetic activation of these neurons. Single cell sequencing reveals that blocking MCH neurons in the LH diminishes osteogenic differentiation of bone marrow stromal cells (BMSCs) and induces senescence. Mechanistically, MCH promotes BMSC differentiation by activating MCHR1 via PKA signaling, and activating MCHR1 by MCH agonists attenuate skeletal senescence in mice. By elucidating a brain‐bone connection that autonomously enhances osteogenesis, these findings uncover the neuroendocrinological mechanisms governing bone mass regulation and protect against skeletal senescence.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Targeting MCH Neuroendocrine Circuit in Lateral Hypothalamus to Protect Against Skeletal Senescence ; day:25 ; month:09 ; year:2024 ; extent:16
Advanced science ; (25.09.2024) (gesamt 16)
- Creator
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Guo, Bin
Zhu, Yong
Lu, Shuai
Chen, Xiangming
Ren, Zhuoqun
Liu, Yuqi
Luo, Hao
Wang, Chao
Yang, Xucheng
Zhu, Jianxi
- DOI
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10.1002/advs.202309951
- URN
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urn:nbn:de:101:1-2409261408399.590104835850
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:23 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Guo, Bin
- Zhu, Yong
- Lu, Shuai
- Chen, Xiangming
- Ren, Zhuoqun
- Liu, Yuqi
- Luo, Hao
- Wang, Chao
- Yang, Xucheng
- Zhu, Jianxi
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