Ophiopogonin D promotes bone regeneration by stimulating CD31(hi)EMCN(hi) vessel formation
Ophiopogonin D promotes bone regeneration by stimulating CD31(hi)EMCN(hi) vessel formation
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麦冬皂苷 D 通过刺激 CD31(hi)EMCN(hi) 血管形成促进骨再生
DOI：
10.1111/cpr.12784
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发表时间：
2020
影响因子：
8.5
通讯作者：
Jiang Tie-Jian
中科院分区：
文献类型：
--
作者：
Yang Mi;Li Chang-Jun;Xiao Ye;Guo Qi;Huang Yan;Su Tian;Luo Xiang-Hang;Jiang Tie-Jian
目的CD31 hiemcnhivascular (CD31，又称PECAM1[血小板与内皮细胞粘附分子1]；EMCN, endoomucin)，其中CD31和endoomucin呈强阳性，促进血管生成和成骨。然而，cd31hiemcn血管在骨再生中的作用尚不清楚。在本研究中，我们研究了cd31hiemcn血管在骨再生过程中的作用。材料和方法我们使用内皮特异性kr<e:1>样因子3 （Klf3）敲除小鼠和麦冬肽素D处理来干扰CD31hiEMCNhivessel的形成。我们通过手术切除小梁骨建立骨再生模型。免疫荧光和微计算机断层扫描（CT）检测cd31hiemcn血管和骨形成。结果scd31hiemcnhivascular参与骨再生过程，内皮特异性icklf3基因敲除小鼠骨再生区域的cd31hiemcnhivascular和骨祖细胞增加，进一步加速骨形成。我们还证明了天然化合物麦冬皂苷D作为KLF3抑制剂，在体外和体内促进血管形成。给药麦冬肽D增加cd31hiemcnhivascular的丰度，加速骨愈合。结论研究结果证实了cd31hiemcnhivascular在骨再生中的重要作用，为治疗骨折或促进骨再生提供了新的靶点。
ObjectivesCD31hiEMCNhivessels (CD31, also known as PECAM1 [platelet and endothelial cell adhesion molecule 1]; EMCN, endomucin), which are strongly positive for CD31 and endomucin, couple angiogenesis and osteogenesis. However, the role of CD31hiEMCNhivessels in bone regeneration remains unknown. In the present study, we investigated the role of CD31hiEMCNhivessels in the process of bone regeneration.Materials and MethodsWe used endothelial‐specific Krüppel like factor 3 (Klf3) knockout mice and ophiopogonin D treatment to interfere with CD31hiEMCNhivessel formation. We constructed a bone regeneration model by surgical ablation of the trabecular bone. Immunofluorescence and micro‐computed tomography (CT) were used to detect CD31hiEMCNhivessels and bone formation.ResultsCD31hiEMCNhivessels participate in the process of bone regeneration, such that endothelial‐specificKlf3knockout mice showed increased CD31hiEMCNhivessels and osteoprogenitors in the bone regeneration area, and further accelerated bone formation. We also demonstrated that the natural compound, ophiopogonin D, acts as a KLF3 inhibitor to promote vessels formation both in vitro and in vivo. Administration of ophiopogonin D increased the abundance of CD31hiEmcnhivessels and accelerated bone healing.ConclusionsOur findings confirmed the important role of CD31hiEmcnhivessels in bone regeneration and provided a new target to treat bone fracture or promote bone regeneration.