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Publication : Region-specific sympatho-adrenergic regulation of specialized vasculature in bone homeostasis and regeneration.

First Author  Xu HK Year  2023
Journal  iScience Volume  26
Issue  9 Pages  107455
PubMed ID  37680481 Mgi Jnum  J:340584
Mgi Id  MGI:7528319 Doi  10.1016/j.isci.2023.107455
Citation  Xu HK, et al. (2023) Region-specific sympatho-adrenergic regulation of specialized vasculature in bone homeostasis and regeneration. iScience 26(9):107455
abstractText  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. In vitro 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.
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