BMP-9 Induced Osteogenic Differentiation of Mesenchymal Stem Cells: Molecular Mechanism and Therapeutic Potential

被引:3
作者
Luther, Gaurav [1 ]
Wagner, Eric R. [1 ]
Zhu, Gaohui [1 ,2 ,3 ]
Kang, Quan [1 ,2 ,3 ]
Luo, Qing [1 ,2 ,3 ]
Lamplot, Joseph [1 ]
Bi, Yang [1 ,2 ,3 ]
Luo, Xiaoji [1 ,4 ,5 ]
Luo, Jinyong [1 ,4 ,5 ]
Teven, Chad [1 ]
Shi, Qiong [1 ,4 ,5 ]
Kim, Stephanie H. [1 ]
Gao, Jian-Li [1 ,6 ]
Huang, Enyi [1 ,7 ]
Yang, Ke [1 ,8 ]
Rames, Richard [1 ]
Liu, Xing [1 ,2 ,3 ]
Li, Mi [1 ,2 ,3 ]
Hu, Ning [1 ,4 ,5 ]
Liu, Hong [1 ,4 ,5 ]
Su, Yuxi [1 ,2 ,3 ]
Chen, Liang [1 ,4 ,5 ]
He, Bai-Cheng [1 ,4 ,5 ]
Zuo, Guo-Wei [1 ,4 ,5 ]
Deng, Zhong-Liang [1 ,4 ,5 ]
Reid, Russell R. [1 ]
Luu, Hue H. [1 ]
Haydon, Rex C. [1 ]
He, Tong-Chuan [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ Chicago, Mol Oncol Lab, Med Ctr, Dept Surg, Chicago, IL 60637 USA
[2] Chongqing Med Univ, Stem Cell Biol & Therapy Lab, Key Lab Pediat Codesignated, Chinese Minist Educ,Childrens Hosp, Chongqing 400016, Peoples R China
[3] Chongqing Med Univ, Chongqing Bur Educ, Childrens Hosp, Chongqing 400016, Peoples R China
[4] Chongqing Med Univ, Key Lab Diagnost Med Designated, Chinese Minist Educ, Chongqing 400016, Peoples R China
[5] Chongqing Med Univ, Affiliated Hosp, Chongqing 400016, Peoples R China
[6] Zhejiang Chinese Med Univ, Inst Mat Med, Hangzhou 310053, Zhejiang, Peoples R China
[7] Chongqing Univ, Sch Bioengn, Chongqing 400016, Peoples R China
[8] Third Mil Med Univ, Dept Cell Biol, Chongqing 400038, Peoples R China
基金
美国国家卫生研究院;
关键词
BMP-9; GDF-2; bone formation; mesenchymal stem cells; fracture healing; bone regeneration; cell-based gene therapy; BONE MORPHOGENETIC PROTEINS; TISSUE GROWTH-FACTOR; PROLIFERATOR-ACTIVATED RECEPTORS; NONVIRAL GENE DELIVERY; OPEN TIBIAL FRACTURES; MUSCLE-DERIVED CELLS; LOOP-HELIX PROTEINS; TGF-BETA; OSTEOBLAST DIFFERENTIATION; IN-VIVO;
D O I
暂无
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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/beta-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/beta-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.
引用
收藏
页码:229 / 240
页数:12
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