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.

Graphic abstract

中文翻译：

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ATP结合盒g1通过Wnt /β-catenin和AMPK信号通路调节成骨作用。

骨髓间充质干细胞（BMSCs）在平衡成骨和脂肪形成中的功能障碍在骨质疏松症的发生和发展中起重要作用。ATP结合盒g1（Abcg1）是否是一种公认​​的成脂调控基因，仍能调节成骨作用，这一点仍然未知。在我们先前的研究中，我们在成骨中鉴定了30个差异表达的基因，并发现这些基因中与成骨呈负相关的Abcg1的表达水平。Abcg1是成熟的脂肪形成调节剂和胆固醇转运蛋白，但在成骨过程中的作用尚不清楚。在这项研究中，我们发现它可以控制成骨，进一步阐明Abcg1在调节成骨细胞分化中的确切作用将有助于提出预防和治疗骨质疏松的新策略。因此，我们建立了表达上调或下调的Abcg1 C3H10T1 / 2和C2C12细胞系，并验证了Abcg1的敲低可增强成骨因子与矮子相关的转录因子2（Runx2）和碱性磷酸酶（ALP）的表达，而Abcg1的过表达则逆转了促进作用。此外，我们证实Abcg1通过Wnt /β-catenin和AMPK信号通路调节成骨作用。综上所述，这些结果表明Abcg1在通过Wnt /β-catenin和AMPK信号通路调节成骨中可能起重要作用，并有望成为骨质疏松症的潜在治疗靶标。而Abcg1过表达逆转了促进作用。此外，我们证实Abcg1通过Wnt /β-catenin和AMPK信号通路调节成骨作用。综上所述，这些结果表明Abcg1在通过Wnt /β-catenin和AMPK信号通路调节成骨中可能起重要作用，并有望成为骨质疏松症的潜在治疗靶标。而Abcg1过表达逆转了促进作用。此外，我们证实Abcg1通过Wnt /β-catenin和AMPK信号通路调节成骨作用。综上所述，这些结果表明Abcg1在通过Wnt /β-catenin和AMPK信号通路调节成骨中可能起重要作用，并有望成为骨质疏松症的潜在治疗靶标。

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