Cysteine Dioxygenase Type 1 Inhibits Osteogenesis by Regulating Wnt Signaling in Primary Mouse Bone Marrow Stromal Cells.
Cysteine Dioxygenase Type 1 Inhibits Osteogenesis by Regulating Wnt Signaling in Primary Mouse Bone Marrow Stromal Cells.
复制标题
1 型半胱氨酸双加氧酶通过调节原代小鼠骨髓基质细胞中的 Wnt 信号传导来抑制骨生成。
DOI：
10.1038/srep19296
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发表时间：
2016-01-14
影响因子：
4.6
通讯作者：
Pae EK
中科院分区：
文献类型：
--
作者：
Zhao X;Deng P;Feng J;Wang Z;Xiang Z;Han X;Bai D;Pae EK
间充质干细胞（Mesenchymal stem cells，MSCs）是一种多能细胞，可分化为脂肪细胞和成骨细胞等多种细胞类型。以前，我们已经表明，半胱氨酸双加氧酶1型（Cdo 1）通过与Pparγ相互作用促进原代小鼠骨髓基质细胞（BMSCs）和3 T3-L1前脂肪细胞的脂肪形成。然而，Cdo 1在骨生成中的作用仍不清楚。在这里，我们证明了Cdo 1的表达升高，在成骨细胞分化的BMSCs在体外。有趣的是，通过siRNA敲低Cdo 1导致成骨相关基因的表达增加，碱性磷酸酶（ALP）活性升高，矿化增强。BMSCs中Cdo 1的过表达抑制成骨。此外，我们发现Cdo 1的过表达损害了Wnt信号传导，并限制了Wnt 3a诱导的成骨转录因子如Runx 2和Dlx 5的表达。总的来说，我们的研究结果表明，Cdo 1抑制BMSCs的成骨分化，通过一个潜在的机制，涉及在Wnt信号减少伴随。
Mesenchymal stem cells (MSCs) are multipotent cells, which can give rise to variety of cell types, including adipocytes and osteoblasts. Previously, we have shown that cysteine dioxygenase type 1 (Cdo1) promoted adipogenesis of primary mouse bone marrow stromal cells (BMSCs) and 3T3-L1 pre-adipocytes via interaction with Pparγ. However, the role of Cdo1 in osteogenesis remains unclear. Here, we demonstrated that expression of Cdo1 was elevated during osteoblastic differentiation of BMSCs in vitro. Interestingly, knockdown of Cdo1 by siRNA led to an increased expression of osteogenic related genes, elevated alkaline phosphatase (ALP) activity, and enhanced mineralization. Overexpression of Cdo1 in BMSCs inversely suppressed the osteogenesis. Furthermore, we found that overexpression of Cdo1 impaired Wnt signaling and restricted the Wnt3a induced expression of osteogenic transcriptional factors, such as Runx2 and Dlx5. Collectively, our findings indicate Cdo1 suppresses osteogenic differentiation of BMSCs, through a potential mechanism which involves in Wnt signaling reduction concomitantly.