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ATP-binding cassette g1 regulates osteogenesis via Wnt/β-catenin and AMPK signaling pathways

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Abstract

The dysfunction of bone marrow mesenchymal stem cells (BMSCs) in balancing osteogenesis and adipogenesis plays an important role in the occurrence and development of osteoporosis. It’s still unknown that whether ATP-binding cassette g1 (Abcg1), a well-proved regulation gene of adipogenesis, regulates osteogenesis. In our previous study, we identified 30 differentially expressed genes in osteogenesis and found the expression level ofAbcg1 negatively related to osteogenesis among these genes. Abcg1 is a well-proven adipogenesis regulator and cholesterol transporter, but it’s role in osteogenesis remained unknown. In this study we found it may control osteogenesis, further elucidating the exact role of Abcg1 in regulating osteoblast differentiation would help propose new strategies to prevent and treat osteoporosis. Therefore, we established Abcg1 up- or down-expressed C3H10T1/2 and C2C12 cell lines and verified that Abcg1 knockdown enhanced expression of osteogenic factors runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP), while Abcg1 overexpression reversed the promoting effect. Furthermore, we confirmed that Abcg1 modulated osteogenesis via the Wnt/β-catenin and AMPK signaling pathways. taken together, these results suggest that Abcg1 may have an important role in regulating osteogenesis via Wnt/β-catenin and AMPK signaling pathways, and expect to be a potential therapeutic target for osteoporosis.

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Funding

This work was support by the Key Department of Minhang District (2017MWTZ02); the Key Department of the Fifth People's Hospital of Shanghai (2017WYZDZK02); the Fifth People's Hospital of Shanghai, Fudan University (2018WYZT01); and the Minhang District Leading Talent Development Funds (Grant No. 201512).

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  1. Lei Zhou and Shiwei Sun contributed equally as first author to this work.

Authors and Affiliations

  1. Department of Orthopedics, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

    Lei Zhou, Shiwei Sun, Tieqi Zhang, Yueming Yu, Liang Xu, Haoran Li, Minghai Wang & Yang Hong

  2. Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

    Lei Zhou

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  1. Lei Zhou
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11033_2020_5800_MOESM1_ESM.tif

Supplementary file1 (TIF 226 kb). Fig S1: The establishment of Abcg1 down-regulated cell lines. A. Protein levels of Abcg1 in control and Abcg1-shRNA groups. B. and C. Measurement of Abcg1 knockdown efficiency in protein or mRNA levels. *P<0.05, **P<0.01, ***P<0.001

11033_2020_5800_MOESM2_ESM.tif

Supplementary file2 (TIF 710 kb). Fig S2: Overexpression of Abcg1 inhibits osteoblast differentiation via Wnt/β-catenin and AMPK signaling pathways. A. The establishment of Abcg1 overexpression C3H10T1/2 cell line. B. Osteogenesis and extracellular were inhibited in the Abcg1-cDNA group, measured using ALP staining, AR-S staining, and relative ALP activity assay. C. Abcg1 upregulation decreased the expression of Runx2 and ALP. D. The expression of β-catenin and phosphorylation of GSK-3β and AMPK were blocked in the Abcg1-cDNA group. *P<0.05, **P<0.01, ***P<0.001

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Zhou, L., Sun, S., Zhang, T. et al. ATP-binding cassette g1 regulates osteogenesis via Wnt/β-catenin and AMPK signaling pathways. Mol Biol Rep 47, 7439–7449 (2020). https://doi.org/10.1007/s11033-020-05800-0

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