Role of glycosaminoglycans of biglycan in BMP-2 signaling.
Role of glycosaminoglycans of biglycan in BMP-2 signaling.
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DOI：
10.1016/j.bbrc.2011.01.022
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发表时间：
2011-02-11
影响因子：
3.1
通讯作者：
Yamauchi M
中科院分区：
文献类型：
--
作者：
Miguez PA;Terajima M;Nagaoka H;Mochida Y;Yamauchi M
最近，我们报道了Biglycan(BGN)促进成骨细胞分化，这一功能部分归因于其对骨形态发生蛋白(BMP)功能的正向调节能力。在这项研究中，我们利用体外和体内模型研究了BGN的糖胺多聚糖(GAG)在这一功能中的作用。BMP-2单独或不联合糖化、部分糖化或去糖化的BGN处理或不处理C2C12肌源性细胞，通过Smad1/5/8磷酸化和碱性磷酸酶(ALP)活性来评价BMP信号和功能的影响。此外，采用大鼠下颌骨缺损模型，研究了BGN的脱糖作用对BMP-2诱导成骨的影响。用糖化、部分糖化或去糖化的BGN单独或与次佳剂量的BMP-2(亚骨形态发生蛋白)复合的胶原支架填充缺损区。在体外实验中，BMP-2与去糖化的BGN联合使用时，BMP信号和功能最强。在大鼠下颌骨实验中，μCT分析显示，只有当亚骨形成蛋白与去糖化的BGN复合时，新生骨才显著增加。这些数据表明，BGN的GAG组分对BGN辅助的BMP功能具有抑制作用。
Recently we have reported that biglycan (BGN) promotes osteoblast differentiation and that this function is due in part to its ability to positively modulate bone morphogenetic protein (BMP) functions. In this study we investigated the role of glycosaminoglycans (GAGs) of BGN in this function using in vitro and in vivo models. C2C12 myogenic cells were treated or untreated with BMP-2 alone or in combination with glycanated, partially glycanated or de-glycanated BGN, and the effects on BMP signaling and function were assessed by Smad1/5/8 phosphorylation and alkaline phosphatase (ALP) activity. Furthermore, the effect of de-glycanation of BGN on BMP-2 induced osteogenesis was investigated employing a rat mandible defect model. The defects were filled with collagen scaffolds loaded with glycanated, partially glycanated or de-glycanated BGN alone or in combination with a sub-optimal dose of BMP-2 (subBMP). In in vitro experiments, BMP signaling and function were the greatest when BMP-2 was combined with de-glycanated BGN among the groups tested. In the rat mandible experiments, μCT analyses revealed that the newly formed bone was significantly increased only when subBMP was combined with de-glycanated BGN. The data indicate that the GAG component of BGN functions as a suppressor for the BGN-assisted BMP function.
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影响因子：
2.9
作者：
Matsuno, Yu-ki;Yamada, Keita;Kakehi, Kazuaki
通讯作者：
Kakehi, Kazuaki
影响因子：
3.1
作者：
Arosarena, O;Collins, W
通讯作者：
Collins, W
影响因子：
4.2
作者：
Boskey, AL;Spevak, L;Rosenberg, L
通讯作者：
Rosenberg, L
影响因子：
4.8
作者：
SCHONHERR, E;WITSCHPREHM, P;KRESSE, H
通讯作者：
KRESSE, H
影响因子：
15.9
作者：
Schaefer, L;Babelova, A;Gröne, HJ
通讯作者：
Gröne, HJ