The antimicrobial peptide LL37 promotes bone regeneration in a rat calvarial bone defect

The antimicrobial peptide LL37 promotes bone regeneration in a rat calvarial bone defect
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DOI:
10.1016/j.peptides.2013.06.001
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发表时间:
2013-08-01
期刊:
影响因子:
3
通讯作者:
Kurihara, Hidemi
Kurihara, Hidemi
中科院分区:
医学3区
文献类型:
--
作者:
Kittaka, Mizuho;Shiba, Hideki;Kurihara, Hidemi

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LL37是一种抗菌肽,在多种类型的细胞中表现出多种生物功能,包括迁移、细胞因子产生、细胞凋亡和血管生成。新生血管和随后的干细胞募集是组织工程治疗必不可少的,包括骨再生。我们假设LL37可以促进成功的骨再生。为了证明这一假设,本研究在大鼠颅骨骨缺损模型中测试了LL37对骨形成的影响。合成LL37明显诱导新生骨形成。有趣的是,在组织再生的早期第7天,在LL37处理的动物中观察到形态学上的成纤维细胞,其中STRO-1(间充质干细胞(MSCs)的标记物)阳性,并在骨缺损区域积聚,其中CD34(内皮细胞的标记物)阳性的细胞也被定位。此外,LL37在体外刺激内皮细胞形成管和MSCs的增殖。这些发现首次证明LL37可以调节血管生成和干细胞募集,促进骨再生。(C) 2013爱思唯尔公司版权所有。
LL37, an antimicrobial peptide, exhibits multiple bio-functions in various types of cells, including migration, cytokine production, apoptosis, and angiogenesis. Neovascularization and the subsequent recruitment of stem cells are essential for tissue engineering therapy, including bone regeneration. We hypothesized that LL37 can facilitate successful bone regeneration. To prove this hypothesis, the present study tested the effects of LL37 on bone formation in a rat calvarial bone defect model. Synthesized LL37 markedly induced newly formed bone. Interestingly, morphologically fibroblastic cells were observed in animals treated with LL37 on day 7, the early stage of tissue regeneration, which were positive for STRO-1, a marker of mesenchymal stem cells (MSCs), and accumulated in the bone defect area where cells positive for CD34, a marker of endothelial cells, were also localized. In addition, LL37 stimulated tube formation by endothelial cells and the proliferation of MSCs in vitro. These findings demonstrated for the first time that LL37 can regulate angiogenesis and the recruitment of stem cells to promote bone regeneration. (C) 2013 Elsevier Inc. All rights reserved.