Department of Biochemistry, Medical School and Research Institute of Clinical Medicine, Chonbuk National University, Jeonju, Jeonbuk, Republic of Korea.
Bone. 2010 May;46(5):1442-8. doi: 10.1016/j.bone.2010.02.004. Epub 2010 Feb 10.
During distraction osteogenesis, new and highly vascularized bone is formed, with angiogenesis preceding osteogenesis. We investigated the possibility that COMP-Ang1, an angiogenic factor, may facilitate bone formation.
Rats were divided into three groups. Control rats underwent tibial distraction without treatment. In the two remaining groups, BSA (100 microg) or COMP-Ang1 (100 microg) were injected transcutaneously into the center of the distraction zone. Using radiographic and histologic analyses, we assessed total bone volume, vascular density, and bone mineral density. Total RNA was prepared from regenerated bone and analyzed for osteogenic marker protein expression using real-time RT-PCR analysis.
Bone formation in the distraction gap progressed more quickly in the COMP-Ang1-treated group than in the BSA-treated group. Histological findings and immunostaining of endothelial cells for factor VIII revealed that Comp-Ang1 group animals exhibited higher levels of vascularity. NanoCT and dual-energy X-ray absorptiometry analyses revealed increased new bone formation along capillaries in the COMP-Ang1 group compared with the BSA group. Runt-related transcription factor 2 and its target genes, including bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the COMP-Ang1 group.
Our results are consistent with previous descriptions of the positive relationship between angiogenesis and osteogenesis. In addition, our results suggest the potential use of COMP-Ang1 as a therapeutic agent for treatment of distracted limbs by enhancing angiogenesis.
在牵张成骨过程中，会形成新的、高度血管化的骨，血管生成先于成骨。我们研究了血管生成因子 COMP-Ang1 是否有助于骨形成的可能性。
将大鼠分为三组。对照组大鼠在不治疗的情况下进行胫骨牵张。在其余两组中，经皮向牵张区中心注射 BSA（100 微克）或 COMP-Ang1（100 微克）。使用影像学和组织学分析，评估总骨体积、血管密度和骨矿物质密度。从再生骨中提取总 RNA，并使用实时 RT-PCR 分析分析成骨标记蛋白的表达。
与 BSA 治疗组相比，COMP-Ang1 治疗组的骨形成在牵张间隙中进展更快。组织学发现和因子 VIII 内皮细胞免疫染色显示，Comp-Ang1 组动物表现出更高的血管生成水平。NanoCT 和双能 X 射线吸收法分析显示，与 BSA 组相比，COMP-Ang1 组在毛细血管周围有更多的新骨形成。Runt 相关转录因子 2 及其靶基因，包括骨涎蛋白、I 型胶原、骨桥蛋白和骨形成蛋白，在 COMP-Ang1 组中显著上调。
我们的结果与先前描述的血管生成与成骨之间的正相关关系一致。此外，我们的结果表明，COMP-Ang1 可能通过增强血管生成作为治疗牵张肢体的治疗剂。
