BMP-9 induced osteogenic differentiation of mesenchymal stem cells: molecular mechanism and therapeutic potential.
BMP-9 induced osteogenic differentiation of mesenchymal stem cells: molecular mechanism and therapeutic potential.
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DOI：
10.2174/156652311795684777
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发表时间：
2011-05
影响因子：
3.6
通讯作者：
G. Luther;Eric R. Wagner;Gao-hui Zhu;Q. Kang;Qing Luo;Joseph D. Lamplot;Yang Bi;Xiaoji Luo;
中科院分区：
文献类型：
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作者：
G. Luther;Eric R. Wagner;Gao-hui Zhu;Q. Kang;Qing Luo;Joseph D. Lamplot;Yang Bi;Xiaoji Luo;
促进成骨分化和有效的骨再生有可能给骨科和肌肉骨骼疾病的治疗带来革命性的变化。间充质干细胞(MSCs)是一种骨髓前体细胞，具有向成骨、成软骨、成肌和成脂等方向分化的能力。沿着这些谱系的分化是一个严格控制的过程，部分受到骨形态发生蛋白(BMPs)的调节。BMP2和BMP7已经被批准用于临床，因为它们的骨诱导特性可以作为影响骨愈合的手术的辅助治疗。BMP-9是研究最少的BMP之一，最近的体外和体内研究证实BMP-9是一种有效的MSCs成骨分化诱导剂。骨形态发生蛋白-9与Wnt/β-catenin等信号通路存在明显的分子串扰，腺病毒表达骨形态发生蛋白-9可增加成骨标志物的表达，诱导成骨样基质形成。此外，BMP-9已被证明在骨形成中与其他信号通路协同作用，包括WNT/β-连环蛋白、胰岛素样生长因子和维甲酸信号通路。这些结果表明，BMP-9应该作为一种有效的骨再生剂，特别是与辅助治疗相结合，用于临床应用，如大型节段性骨缺损、骨不连和/或脊柱融合。
Promoting osteogenic differentiation and efficacious bone regeneration have the potential to revolutionize the treatment of orthopaedic and musculoskeletal disorders. Mesenchymal Stem Cells (MSCs) are bone marrow progenitor cells that have the capacity to differentiate along osteogenic, chondrogenic, myogenic, and adipogenic lineages. Differentiation along these lineages is a tightly controlled process that is in part regulated by the Bone Morphogenetic Proteins (BMPs). BMPs 2 and 7 have been approved for clinical use because their osteoinductive properties act as an adjunctive treatment to surgeries where bone healing is compromised. BMP-9 is one of the least studied BMPs, and recent in vitro and in vivo studies have identified BMP-9 as a potent inducer of osteogenic differentiation in MSCs. BMP-9 exhibits significant molecular cross-talk with the Wnt/ β-catenin and other signaling pathways, and adenoviral expression of BMP-9 in MSCs increases the expression of osteogenic markers and induces trabecular bone and osteiod matrix formation. Furthermore, BMP-9 has been shown to act synergistically in bone formation with other signaling pathways, including Wnt/ β-catenin, IGF, and retinoid signaling pathways. These results suggest that BMP-9 should be explored as an effective bone regeneration agent, especially in combination with adjuvant therapies, for clinical applications such as large segmental bony defects, non-union fractures, and/or spinal fusions.