Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery
Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery
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DOI：
10.1038/sj.gt.3302298
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发表时间：
2004-09-01
期刊：
影响因子：
5.1
通讯作者：
He, TC
中科院分区：
文献类型：
--
作者：
Kang, Q;Sun, MH;He, TC
有效的骨再生可以彻底改变骨骼和肌肉骨骼疾病的临床治疗。虽然几种骨形态发生蛋白（BMP）（主要是BMP-2和BMP-7）已被证明可以诱导骨形成，但目前尚不清楚目前使用的BMP是否代表最具成骨性的蛋白。直到最近，所有BMP的成骨活性的综合分析一直受到阻碍的事实，重组蛋白要么是没有生物活性或不可用的所有BMP。在这项研究中，我们使用重组腺病毒表达的14种类型的骨形成蛋白（AdBMPs），并证明，除了目前使用的BMP-2和BMP-7，BMP-6和BMP-9有效地诱导原位祖细胞或病毒载体注射到无胸腺小鼠的四头肌。放射学和组织学评价表明，BMP-6和BMP-9在多个时间点诱导最稳健和成熟的骨化。骨形成的负调节剂BMP-3显示出有效抑制由BMP-2、BMP-6和BMP-7诱导的原位骨化。然而，BMP-3对BMP-9诱导的骨形成没有抑制作用，这表明BMP-9可能以不同的方式抑制成骨信号。我们的研究结果表明，BMP-6和BMP-9可能代表更有效的骨再生成骨因子。
Efficacious bone regeneration could revolutionize the clinical management of bone and musculoskeletal disorders. Although several bone morphogenetic proteins (BMPs) (mostly BMP-2 and BMP-7) have been shown to induce bone formation, it is unclear whether the currently used BMPs represent the most osteogenic ones. Until recently, comprehensive analysis of osteogenic activity of all BMPs has been hampered by the fact that recombinant proteins are either not biologically active or not available for all BMPs. In this study, we used recombinant adenoviruses expressing the 14 types of BMPs (AdBMPs), and demonstrated that, in addition to currently used BMP-2 and BMP-7, BMP-6 and BMP-9 effectively induced orthotopic progenitors or the viral vectors were injected into the quadriceps of athymic mice. Radiographic and histological evaluation demonstrated that BMP-6 and BMP-9 induced the most robust and mature ossification at multiple time points. BMP-3, a negative regulator of bone formation, was shown to effectively inhibit orthotopic ossification induced by BMP-2, BMP-6, and BMP-7. However, BMP-3 exerted no inhibitory effect on BMP-9-induced bone formation, suggesting that BMP-9 may transduce osteogenic signaling differently. Our findings suggest that BMP-6 and BMP-9 may represent more effective osteogenic factors for bone regeneration.