福克斯O1
自噬
成骨细胞
生物
细胞生物学
下调和上调
信号转导
体外
细胞凋亡
生物化学
基因
蛋白激酶B
作者
Yixuan Jiang,Wenqiong Luo,Feng Zhou,Ping Gong,Xiong Yu
出处
期刊:Cell Cycle
[Informa]
日期:2022-12-12
卷期号:22 (7): 829-840
被引量:2
标识
DOI:10.1080/15384101.2022.2155443
摘要
Autophagy is essential for the maintenance of intracellular homeostasis, implicated in various biological processes. Forkhead box protein O1 (FOXO1) is regarded as a key mediator regulating skeletal development. Recent studies indicate that FOXO1 has a multifaceted role in autophagy regulation and dysregulation. Here, we aimed to elucidate the role of FOXO1-autophagy axis in osteogenesis. Osteoblast conditional Foxo1-knockout mice (Foxo1OB−/−, KO) and FOXO1 lentivirus overexpression (Len-FoxO1) model were constructed in vivo. Primary osteoblasts were isolated from KO and their wild-type (WT) littermates. And we also applied overexpression lentivirus to investigate the effects of FOXO1 in vitro. Using Micro-CT, fluorescence labeling detection, real-time qPCR and western blot analyses, we found that bone formation was promoted in Len-FOXO1 mice, which was impaired in KO group. Similarly, FOXO1 overexpression enhanced proliferation, migration and differentiation of osteoblasts, while FOXO1 ablation resulted in poor biological functions of osteoblasts. Through the investigation of autophagic process using mRFP-GFP-LC3 fluorescence labeling and co-immunoprecipitation, we observed that overexpression of FOXO1 initiated autophagy induction, with enhanced FOXO1 interaction with autophagy-related protein 7 (ATG7). On the contrary, FOXO1 knockout in osteoblasts impeded FOXO1-ATG7 conjugation, leading to impaired autophagic activity. Furthermore, inhibition of autophagy by chloroquine (CQ) could reverse favorable influences in bone formation induced by FOXO1 overexpression. Our findings confirmed that FOXO1 was an important regulator of bone formation and autophagy might be part of the underlying mechanisms, offering a significant avenue for the potential strategy in the treatment of bone-related disorders.
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