Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells

Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells
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DOI:
10.1002/jor.20359
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发表时间:
2007-05-01
影响因子:
2.8
通讯作者:
He, Tong-Chuan
He, Tong-Chuan
中科院分区:
医学3区
文献类型:
--
作者:
Luu, Hue H.;Song, Wen-Xin;He, Tong-Chuan

文献摘要

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有效的骨再生可以彻底改变许多骨骼和肌肉骨骼疾病的临床治疗方法。骨形态发生蛋白(BMPs)可以调节间充质干细胞向软骨、骨、腱/韧带和脂肪等方向分化。早期的数据证明了rh BMP2和rh BMP7/OP-1的成骨潜力。然而,在这项总结了我们最近几项研究的工作之前,还没有对所有BMP的相对成骨活性进行全面的分析。利用表达14个BMPs的重组腺病毒,我们已经证明,除了BMP2和BMP7,BMP6和BMP9在体外和体内都具有最高的成骨活性。我们进一步证明了几种BMP在成骨分化中可能发挥协同作用,成骨BMPs在成骨分化过程中产生了一组不同的分子指纹。报道的工作应该会扩大我们目前对BMP在成骨分化过程中功能的理解。可以想象,成骨BMPs(即BMP2、4、6、7和9)可以在它们之间和/或与其他成骨能力较低的BMPs之间形成协同对,以在临床环境中有效地再生骨。(C)2007年整形外科研究会。
Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone morphogenetie proteins (BMPs) can regulate the differentiation of mesenchymal stem cells into cartilage, bone, tendon/ligament, and fat lineages. Early data documented the osteogenic potential of rhBMP2 and rhBMP7/OP-1. However, prior to this work that summarized several of our recent studies, no comprehensive analysis had been undertaken to characterize relative osteogenie activity of all BMPs. Using recombinant adenoviruses expressing 14 BMPs, we have demonstrated that, besides BMP2 and BMP7, BMP6 and BMP9 exhibit the highest osteogenic activity both in vitro and in vivo. We further demonstrated that several BMPs may exert synergistic effect on osteogenic differentiation, and that osteogenie BMPs produce a distinct set of molecular fingerprints during osteogenic differentiation. The reported work should expand our current understanding of BMP functions during osteogenic differentiation. It is conceivable that osteogenic BMPs (i.e., BMP2, 4, 6, 7, and 9) may be used to formulate synergistic pairs among themselves and/or with other less osteogenic BMPs for efficacious bone regeneration in clinical settings. (c) 2007 Orthopaedic Research Society.