骨骼稳态与再生中特定区域对特殊脉管系统的交感 - 肾上腺素能调节。
Region-specific sympatho-adrenergic regulation of specialized vasculature in bone homeostasis and regeneration.
作者信息
Xu Hao-Kun, Liu Jie-Xi, Zheng Chen-Xi, Liu Lu, Ma Chao, Tian Jiong-Yi, Yuan Yuan, Cao Yuan, Xing Shu-Juan, Liu Si-Ying, Li Qiang, Zhao Ya-Juan, Kong Liang, Chen Yong-Jin, Sui Bing-Dong
机构信息
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Department of Oral Anatomy and Physiology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
出版信息
iScience. 2023 Jul 22;26(9):107455. doi: 10.1016/j.isci.2023.107455. eCollection 2023 Sep 15.
Type H vessels couple angiogenesis with osteogenesis, while sympathetic cues regulate vascular and skeletal function. The crosstalk between sympathetic nerves and type H vessels in bone remains unclear. Here, we first identify close spatial connections between sympathetic nerves and type H vessels in bone, particularly in metaphysis. Sympathoexcitation, mimicked by isoproterenol (ISO) injection, reduces type H vessels and bone mass. Conversely, beta-2-adrenergic receptor (ADRB2) deficiency maintains type H vessels and bone mass in the physiological condition. experiments reveal indirect sympathetic modulation of angiogenesis via paracrine effects of mesenchymal stem cells (MSCs), which alter the transcription of multiple angiogenic genes in endothelial cells (ECs). Furthermore, Notch signaling in ECs underlies sympathoexcitation-regulated type H vessel formation, impacting osteogenesis and bone mass. Finally, propranolol (PRO) inhibits beta-adrenergic activity and protects type H vessels and bone mass against estrogen deficiency. These findings unravel the specialized neurovascular coupling in bone homeostasis and regeneration.
H型血管将血管生成与骨生成联系起来，而交感神经信号调节血管和骨骼功能。骨骼中交感神经与H型血管之间的相互作用尚不清楚。在这里，我们首先确定了骨骼中交感神经与H型血管之间紧密的空间联系，特别是在干骺端。注射异丙肾上腺素（ISO）模拟的交感神经兴奋会减少H型血管和骨量。相反，β-2-肾上腺素能受体（ADRB2）缺乏在生理条件下维持H型血管和骨量。实验揭示了交感神经通过间充质干细胞（MSC）的旁分泌作用对血管生成的间接调节，这会改变内皮细胞（EC）中多个血管生成基因的转录。此外，EC中的Notch信号是交感神经兴奋调节的H型血管形成的基础，影响骨生成和骨量。最后，普萘洛尔（PRO）抑制β-肾上腺素能活性，并保护H型血管和骨量免受雌激素缺乏的影响。这些发现揭示了骨骼稳态和再生中特殊的神经血管耦合。
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