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Contrary Roles of Wnt/β-Catenin Signaling in BMP9-Induced Osteogenic and Adipogenic Differentiation of 3T3-L1 Preadipocytes

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Abstract

Our previous study revealed that 3T3-L1 preadipocytes can differentiate to either osteoblasts or adipocytes in response to bone morphogenic protein 9 (BMP9). In the present study, we try to further investigate whether the Wnt/β-catenin signaling plays a crucial role in this process. It was found that BMP9 effectively activated the Wnt/β-catenin signaling, and induced the expression levels of certain canonical Wnt ligands and their receptors in preadipocytes. Exogenous expression of β-catenin, Wnt1, Wnt3a, and Wnt10b potentiated BMP9-induced alkaline phosphatase (ALP) activity, while β-catenin knockdown or Dickkopf 1 (Dkk1) diminished BMP9-induced ALP activity. Moreover, it was demonstrated that β-catenin overexpression promoted BMP9-induced mineralization, and increased the expression levels of late osteogenic markers osteopontin and osteocalcin. Furthermore, β-catenin inhibited BMP9-induced lipid accumulation and the adipogenic marker adipocyte fatty acid binding protein (aP2). The cell-implantation assay results identified that β-catenin not only augmented BMP9-induced ectopic bone formation, but also blocked adipogenesis in vivo. Mechanistically, it was found that β-catenin and BMP9 synergistically stimulated the osteogenic transcription factors runt-related transcription factor 2 (Runx2) and Osterix (OSX). However, BMP9-induced adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer-binding protein α (C/EBPα), were inhibited by β-catenin. Therefore, these findings suggested that the Wnt/β-catenin signaling, potentially via the modulation of osteogenic and adipogenic transcriptional factors, exerts an opposite effect on BMP9-induced osteogenic and adipogenic differentiation in preadipocytes.

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Acknowledgements

We thank Dr. TC He (University of Chicago Medical Center, USA) for providing recombinant adenoviruses and pTOP-luc reporter plasmid. The present study was supported by Natural Science Foundation of China (grant no. 81601895).

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  1. Department of Orthopaedic Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China

    Kailu Liang, Yu Du, Liang Chen, Liyuan Wang, Ruidong Li, Zhengjian Yan & Yang Liu

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  1. Kailu Liang
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  2. Yu Du
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  3. Liang Chen
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Contributions

Y.L., K.L.L., and L.C. conceived and designed the study. K.L.L., R.D.L., Z.J.Y., and L.Y.W. performed the experiments. Y.L. and K.L.L. collected and analyzed the data. Y.L. wrote the manuscript.

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Correspondence to Yang Liu.

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Liang, K., Du, Y., Chen, L. et al. Contrary Roles of Wnt/β-Catenin Signaling in BMP9-Induced Osteogenic and Adipogenic Differentiation of 3T3-L1 Preadipocytes. Cell Biochem Biophys 78, 347–356 (2020). https://doi.org/10.1007/s12013-020-00935-0

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