Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis.
Osteoclasts protect bone blood vessels against senescence through the angiogenin/plexin-B2 axis.
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DOI：
10.1038/s41467-021-22131-1
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发表时间：
2021-03-23
影响因子：
16.6
通讯作者：
Wan M
中科院分区：
文献类型：
--
作者：
Liu X;Chai Y;Liu G;Su W;Guo Q;Lv X;Gao P;Yu B;Ferbeyre G;Cao X;Wan M
合成糖皮质激素(GCs)是治疗儿童慢性炎症和自身免疫性疾病的最有效的治疗方法之一，对生长中的骨骼有不利影响。GCS抑制正在生长的骨骼中的血管生成，但其潜在机制尚不清楚。在这里，我们发现在年轻的小鼠GC治疗诱导血管内皮细胞衰老的长骨干骺端，内皮细胞衰老的抑制改善了GC受损的骨血管生成与耦合的成骨。我们发现血管生成素(Ang)是破骨细胞分泌的一种具有促血管生成活性的核糖核酸酶，是保护邻近血管细胞免受衰老的关键因素。Ang通过Plexin-B2(PLXNB2)介导的核糖体RNA(RRNA)转录维持内皮细胞的增殖活性。GC治疗通过抑制干骺端破骨细胞的形成来抑制Ang的产生，导致内皮细胞rRNA转录受损和随后的细胞衰老。这些发现揭示了干骺端血管衰老在调节GCs对生长骨骼的作用中的作用，并建立了Ang/PLXNB2轴作为破骨细胞-血管在骨骼血管生成中相互作用的分子基础。糖皮质激素(GCs)抑制骨血管生成，影响骨发育，但其机制尚不清楚。在这里，作者表明，GC通过抑制破骨细胞分泌血管生成素，通过内皮丛蛋白B2损害血管生成，导致不成对的骨生长，从而诱导骨发育过程中的血管细胞衰老。
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, resulting in impaired endothelial cell rRNA transcription and subsequent cellular senescence. These findings reveal the role of metaphyseal blood vessel senescence in mediating the action of GCs on growing skeleton and establish the ANG/PLXNB2 axis as a molecular basis for the osteoclast-vascular interplay in skeletal angiogenesis. Glucocorticoids (GCs) inhibit bone angiogenesis and affect bone development, but the underlying mechanisms remain unclear. Here, the authors show that GCs induce vascular cell senescence during bone development by inhibiting angiogenin secretion from osteoclasts, impairing angiogenesis via endothelial Plexin B2, resulting in unpaired bone growth.
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影响因子：
3.3
作者：
Freund A;Laberge RM;Demaria M;Campisi J
通讯作者：
Campisi J
DOI：
10.1111/j.1749-6632.2011.06287.x
发表时间：
2011-01-01
期刊：
SKELETAL BIOLOGY AND MEDICINE II: BONE AND CARTILAGE HOMEOSTASIS AND BONE DISEASE
影响因子：
--
作者：
Blair, Harry C.;Robinson, Lisa J.;Zaidi, Mone
通讯作者：
Zaidi, Mone
影响因子：
1.7
作者：
Basiji, David A.;Ortyn, William E.;Morrissey, Philip
通讯作者：
Morrissey, Philip
影响因子：
4.7
作者：
Crivello, Martin;O'Riordan, Saidhbhe L.;Prehn, Jochen H. M.
通讯作者：
Prehn, Jochen H. M.
影响因子：
4.1
作者：
Berendsen AD;Olsen BR
通讯作者：
Olsen BR