Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Dent Res. 2021 Aug;100(9):983-992. doi: 10.1177/00220345211002120. Epub 2021 Mar 25.
Type H vessel is a specific vessel subtype that is strongly positive for CD31 and endomucin (CD31Emcn). It has already been identified that it can tightly regulate the coupling of angiogenesis and osteogenesis in the long bone of mice and human beings. The long bone is formed through endochondral ossification, which is the same type of process happening in mandibular condyle. Although the ossification of long bone and mandibular condyle has the same developmental process, the existence of type H vessels in the mouse condyle remains unclear. To address this, we identified that abundant type H vessels existed in the subchondral bone of the mouse condylar head and endosteum of the mouse condylar neck. Meanwhile, immunofluorescence imaging of the condyles in different ages of male C57BL/6J mice demonstrated that type H vessels decreased while aging. Furthermore, we validated a positive correlation between type H vessels and Osterix osteoprogenitors in the condyle induced by mandibular advancement. Mechanistically, we confirmed that deferoxamine mesylate, which promoted the proliferation of type H endothelial cells by activating hypoxia-inducible factor 1α (HIF-1α) signaling pathways, largely prevented the osteopenia in the condyle induced by botulinum toxin type A. Collectively, these results demonstrate that in the mouse condyle, type H vessels in areas of high function positively correlate with bone formation. In addition, we show a novel influence of HIF-1α signaling on osteogenesis via an increase in type H vessels. In conclusion, promoting angiogenesis of type H vessels is a promising strategy for the therapeutic improvement of osteogenesis in mandibular condyle.
H 型血管是一种特定的血管亚型,其对 CD31 和内粘蛋白(CD31Emcn)呈强阳性。已经发现,它可以紧密调节小鼠和人类长骨中血管生成和骨生成的偶联。长骨是通过软骨内骨化形成的,这与下颌骨髁突的过程相同。尽管长骨和下颌骨的骨化具有相同的发育过程,但在小鼠髁突中是否存在 H 型血管尚不清楚。为了解决这个问题,我们发现大量 H 型血管存在于小鼠髁突头的软骨下骨和小鼠髁突颈部的骨内膜中。同时,对不同年龄雄性 C57BL/6J 小鼠髁突的免疫荧光成像显示,随着年龄的增长,H 型血管减少。此外,我们验证了在由下颌前伸诱导的髁突中,H 型血管与 Osterix 成骨前体细胞呈正相关。从机制上讲,我们证实甲磺酸去铁胺通过激活低氧诱导因子 1α(HIF-1α)信号通路促进 H 型内皮细胞的增殖,在很大程度上防止了肉毒毒素 A 诱导的髁突骨量减少。总之,这些结果表明,在小鼠髁突中,高功能区域的 H 型血管与骨形成呈正相关。此外,我们通过增加 H 型血管显示了 HIF-1α 信号对成骨的新影响。总之,促进 H 型血管的血管生成是改善下颌骨髁突成骨的有前途的治疗策略。