Cysteine Dioxygenase Type 1 Inhibits Osteogenesis by Regulating Wnt Signaling in Primary Mouse Bone Marrow Stromal Cells.

Xuefeng Zhao,Ding Bai,Peng Deng,Zheng Wang,Eung-Kwon Pae,Zichao Xiang,Jie Feng,Xianglong Han

doi:10.1038/srep19296

Xuefeng Zhao, Ding Bai + Show 6 more

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https://doi.org/10.1038/srep19296

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Abstract

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.

Highlights

Mammalian cysteine dioxygenase type 1 (Cdo1) is an essential enzyme for taurine biosynthesis by catalyzing the oxidation of cysteine to cysteine sulfinic acid[19]
We used two specific siRNAs to knockdown the expression of Cdo[1] in bone marrow stromal cells (BMSCs), and the knockdown efficiency in the presence or absence of osteogenic stimulus was assessed by Reverse Transcription-PCR (RT-PCR) (Fig. 2A)
We have found that the expression of Cdo[1] was up-regulated during osteogenic differentiation of BMSCs in vitro

Summary

Introduction

Mammalian cysteine dioxygenase type 1 (Cdo1) is an essential enzyme for taurine biosynthesis by catalyzing the oxidation of cysteine to cysteine sulfinic acid[19]. Via interaction with peroxisome proliferator-activated receptor gamma (Pparγ )[21]. Given these findings, and an inverse relationship between osteogenesis and adipogenesis, we hypothesize that Cdo[1] may inhibit osteoblastic differentiation of MSC. An inverse relationship between osteogenesis and adipogenesis, we hypothesize that Cdo[1] may inhibit osteoblastic differentiation of MSC To address this hypothesis, in this study, we investigated the expression pattern of Cdo[1] during osteogenic differentiation of BMSCs, and examined the effects of depletion of Cdo[1] and overexpression of Cdo[1] on this osteogenic process. Our findings indicate Cdo[1] suppresses osteogenesis via inhibition of Wnt signaling

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