Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function.

Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function.
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DOI:
10.1038/s41598-018-25279-x
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发表时间:
2018-05-04
期刊:
影响因子:
4.6
通讯作者:
Yamauchi M
Yamauchi M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jongwattanapisan P;Terajima M;Miguez PA;Querido W;Nagaoka H;Sumida N;Gurysh EG;Ainslie KM;Pleshko N;Perera L;Yamauchi M

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我们已经报道了重组双糖链(BGN)核心蛋白通过增强骨形态发生蛋白(BMP)-2的功能来促进体内骨形成。本研究的目的是确定BGN核心蛋白内促进BMP-2成骨功能的特定结构域(“效应器”)。因此,我们产生了各种重组和合成肽对应的几个领域的BGN,并测试其对BMP-2的功能在体外的影响。结果表明,BGN富含亮氨酸重复序列2-3结构域(LRR 2 -3)显著增强BMP-2诱导的Smad 1/5/9磷酸化、成骨基因表达和肌源性C2 C12细胞碱性磷酸酶活性。此外,向成骨细胞MC 3 T3-E1中添加LRR 2 -3加速体外矿化,而不损害矿物质和基质的质量。这些数据表明,LRR 2 -3至少部分地负责BGN增强BMP-2成骨功能的能力,并且它可能对骨组织再生有用。
We have reported that recombinant biglycan (BGN) core protein accelerates bone formation in vivo by enhancing bone morphogenetic protein (BMP)-2 function. The purpose of the present study was to identify the specific domain (“effector”) within the BGN core protein that facilitates BMP-2 osteogenic function. Thus, we generated various recombinant and synthetic peptides corresponding to several domains of BGN, and tested their effects on BMP-2 functions in vitro. The results demonstrated that the leucine-rich repeats 2–3 domain (LRR2-3) of BGN significantly enhanced the BMP-2 induced Smad1/5/9 phosphorylation, osteogenic gene expression, and alkaline phosphatase activity in myogenic C2C12 cells. Furthermore, addition of LRR2-3 to osteoblastic MC3T3-E1 cells accelerated in vitro mineralization without compromising the quality of the mineral and matrix. These data indicate that LRR2-3 is, at least in part, responsible for BGN’s ability to enhance BMP-2 osteogenic function, and it could be useful for bone tissue regeneration.
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