作者
Xiaonan Liu, Yu Chai, Guanqiao Liu, Weiping Su, Qiaoyue Guo, Xiao Lv, Peisong Gao, Bin Yu, Gerardo Ferbeyre, Xu Cao, Mei Wan
发表日期
2021/3/23
期刊
Nature communications
卷号
12
期号
1
页码范围
1832
出版商
Nature Publishing Group UK
简介
Synthetic glucocorticoids (GCs), one of the most effective treatments for chronic inflammatory and autoimmune conditions in children, have adverse effects on the growing skeleton. GCs inhibit angiogenesis in growing bone, but the underlying mechanisms remain unclear. Here, we show that GC treatment in young mice induces vascular endothelial cell senescence in metaphysis of long bone, and that inhibition of endothelial cell senescence improves GC-impaired bone angiogenesis with coupled osteogenesis. We identify angiogenin (ANG), a ribonuclease with pro-angiogenic activity, secreted by osteoclasts as a key factor for protecting the neighboring vascular cells against senescence. ANG maintains the proliferative activity of endothelial cells through plexin-B2 (PLXNB2)-mediated transcription of ribosomal RNA (rRNA). GC treatment inhibits ANG production by suppressing osteoclast formation in metaphysis …
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