Modulation of matrix mineralization by Vwc2-like protein and its novel splicing isoforms.
Modulation of matrix mineralization by Vwc2-like protein and its novel splicing isoforms.
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DOI：
10.1016/j.bbrc.2011.12.075
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发表时间：
2012-02-03
影响因子：
3.1
通讯作者：
Mochida, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Ohyama, Yoshio;Katafuchi, Michitsuna;Almehmadi, Ahmed;Venkitapathi, Sundharamani;Jaha, Haytham;Ehrenman, Jason;Morcos, Joseph;Aljamaan, Reem;Mochida, Yoshiyuki
关键词：
在寻找新的半胱氨酸结蛋白（cysteine knot protein，CKP）家族成员的过程中，我们发现了一个新的基因Vwc 2l及其转录变体Vwc 2l-1、Vwc 2l-2和Vwc 2l-3。根据推导的氨基酸序列，Vwc 2l-1具有一个信号肽和两个富含半胱氨酸（CR）的结构域，而Vwc 2l-2缺少部分第二CR结构域，Vwc 2l-3都是CR结构域。虽然已经报道了在脑中主要观察到Brorin样的表达，但是我们发现在更普遍的组织中检测到Vwc 21转录变体。在成骨细胞中，在基质矿化阶段观察到Vwc 2l表达的诱导。当Vwc 2l稳定转染到成骨细胞中时，与对照组相比，表达Vwc 2l的克隆中的基质矿化明显加速，表明Vwc 2l蛋白对成骨细胞功能的调节作用。进一步研究了Vwc 2l调节的机制，我们发现Osterix（关键成骨标志物之一）的表达通过添加所有Vwc 2l同种型蛋白质而显著增加。综上所述，Vwc 2l是一种新型分泌蛋白，其可能通过TGF-β超家族生长因子信号通路调节Osterix表达来促进基质矿化。我们的数据可能提供了这种新的CKP成员在骨中的生物学功能的机制见解，并进一步提出了一种新的方法来增强成骨细胞的功能，这使得能够加速骨形成，再生和愈合。
In search of new cysteine knot protein (CKP) family members, we found a novel gene called von Willebrand factor C domain-containing protein 2-like (Vwc2l, also known as Brorin-like) and its transcript variants (Vwc2l-1, Vwc2l-2 and Vwc2l-3). Based on the deduced amino acid sequence, Vwc2l-1 has a signal peptide and 2 cysteine-rich (CR) domains, while Vwc2l-2 lacks a part of 2nd CR domain and Vwc2l-3 both CR domains. Although it has been reported that the expression of Brorin-like was predominantly observed in brain, we found that Vwc2l transcript variants were detected in more ubiquitous tissues. In osteoblasts, the induction of Vwc2l expression was observed at matrix mineralization stage. When Vwc2l was stably transfected into osteoblasts, the matrix mineralization was markedly accelerated in Vwc2l-expressing clones compared to that in the control, indicating the modulatory effect of Vwc2l protein on osteoblastic cell function. The mechanistic insight of Vwc2l-modulation was further investigated and we found that the expression of Osterix, one of the key osteogenic markers, was significantly increased by addition of all Vwc2l isoform proteins. Taken together, Vwc2l is a novel secreted protein that promotes matrix mineralization by modulating Osterix expression likely through TGF-β superfamily growth factor signaling pathway. Our data may provide mechanistic insights into the biological functions of this novel CKP member in bone and further suggest a novel approach to enhance osteoblast function, which enables to accerelate bone formation, regeneration and healing.
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DOI：
10.1016/j.matbio.2008.11.003
发表时间：
2009-01
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Mochida Y;Parisuthiman D;Pornprasertsuk-Damrongsri S;Atsawasuwan P;Sricholpech M;Boskey AL;Yamauchi M
通讯作者：
Yamauchi M
影响因子：
64.8
作者：
Imamura, T;Takase, M;Miyazono, K
通讯作者：
Miyazono, K
影响因子：
4.8
作者：
Koike, Naomi;Kassai, Yoshiaki;Itoh, Nobuyuki
通讯作者：
Itoh, Nobuyuki
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
6.9
作者：
Fisher, MC;Li, YC;Kosher, RA
通讯作者：
Kosher, RA