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骨形成肽诱导 BMP-7 前肽区的成骨作用。

Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7.

机构信息

Heart Research Center and Cardiovascular Research Institute of Chonnam National University, Gwangju, Republic of Korea.

出版信息

Biomaterials. 2012 Oct;33(29):7057-63. doi: 10.1016/j.biomaterials.2012.06.036. Epub 2012 Jul 15.

DOI:10.1016/j.biomaterials.2012.06.036
PMID:22795855
Abstract

Osteoporosis is a reduction in skeletal mass due to an imbalance between bone formation and bone resorption. Many researchers have tried to develop adjuvants as specific suppressors of bone resorption and stimulators of bone formation for therapeutic purposes in patients with osteoporosis. Therefore, specific stimulators on bone formation are one of therapeutic significance in the treatment of osteoporosis. Until now, the regulation of bone generation has been the focus of bone morphogenetic protein-7 (BMP-7) investigation from mature form. However, new peptides from immature form which has osteogenic activity has not been reported and developments of these proteins are still remained. In this study, we found a new peptide sequence, called bone forming peptide-1 (BFP-1) and have more high activities of osteogenic differentiation compared with BMP-7. BFP-1-treated multipotent bone marrow stromal stem cells (MBSCs) induced the expression levels and activity of alkaline phosphatase (ALP). Moreover, BFP-1 enhanced the levels of CD44, CD47 and CD51 expression as well as increased Ca(2+) content in MBSCs. In current study, radiography at 8 weeks revealed that BFP-1 pretreated-MBSC transplanted animals had strongly increased bone formation compared to that in the BMP-7 pretreated MBSC transplanted animals. Our finding indicates a new insight into peptides from the immature region of BMP-7 can also be useful in the development of adjuvant therapies for bone-related diseases.

摘要

骨质疏松症是由于骨形成和骨吸收之间的失衡导致的骨骼质量减少。许多研究人员试图开发佐剂,作为骨质疏松症患者治疗中骨吸收的特异性抑制剂和骨形成的刺激剂。因此,针对骨形成的特异性刺激剂是治疗骨质疏松症的治疗意义之一。到目前为止,骨生成的调节一直是骨形态发生蛋白-7(BMP-7)从成熟形式研究的重点。然而,尚未报道具有成骨活性的不成熟形式的新肽,这些蛋白质的开发仍在进行中。在这项研究中,我们发现了一种新的肽序列,称为成骨肽-1(BFP-1),与 BMP-7 相比,其具有更高的成骨分化活性。BFP-1 处理后的多能骨髓基质干细胞(MBSCs)诱导碱性磷酸酶(ALP)的表达水平和活性增加。此外,BFP-1 增强了 MBSCs 中 CD44、CD47 和 CD51 的表达水平以及 Ca(2+)含量。在当前的研究中,8 周的放射照相显示,与 BMP-7 预处理 MBSC 移植动物相比,BFP-1 预处理 MBSC 移植动物的骨形成明显增加。我们的发现表明,BMP-7 不成熟区域的肽也可以为骨相关疾病的辅助治疗的发展提供新的见解。

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