Department of Orthopedics, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Mol Biol Rep. 2020 Oct;47(10):7439-7449. doi: 10.1007/s11033-020-05800-0. Epub 2020 Sep 14.
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.
骨髓间充质干细胞(BMSCs)成骨和成脂平衡失调在骨质疏松症的发生和发展中起重要作用。尽管 ABCG1(脂肪生成的一个有充分证据的调节基因)是否调节成骨作用尚不清楚。在我们之前的研究中,我们在成骨过程中鉴定了 30 个差异表达基因,并发现这些基因中 Abcg1 的表达水平与成骨呈负相关。ABCG1 是脂肪生成的一个有充分证据的调节因子和胆固醇转运蛋白,但它在成骨中的作用尚不清楚。在这项研究中,我们发现它可能控制着成骨作用,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症的新策略。因此,我们建立了 ABCG1 上调或下调的 C3H10T1/2 和 C2C12 细胞系,并验证了 Abcg1 敲低增强了成骨因子 runt 相关转录因子 2(Runx2)和碱性磷酸酶(ALP)的表达,而 Abcg1 过表达则逆转了这种促进作用。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 可能通过 Wnt/β-catenin 和 AMPK 信号通路在调节成骨作用中起重要作用,并有望成为骨质疏松症的潜在治疗靶点。