Wang Ying, Yu Xueying, Sun Fenyong, Fu Yan, Hu Tingting, Shi Qiqing, Man Qiuhong
Department of Clinical Laboratory, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Department of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Redox Rep. 2025 Dec;30(1):2435241. doi: 10.1080/13510002.2024.2435241. Epub 2024 Dec 31.
Bone remodeling imbalance contributes to osteoporosis. Though current medications enhance osteoblast involvement in bone formation, the underlying pathways remain unclear. This study was aimed to explore the pathways involved in bone formation by osteoblasts, we investigate the protective role of glycolysis and N6-methyladenosine methylation (m6A) against oxidative stress-induced impairment of osteogenesis in MC3T3-E1 cells.
We utilized a concentration of 200 μM hydrogen peroxide (HO) to establish an oxidative damage model of MC3T3-E1 cells. Subsequently, we examined the alterations in the m6A methyltransferases (METTL3, METTL14), glucose transporter proteins (GLUT1, GLUT3) and validated m6A methyltransferase overexpression in vitro and in an osteoporosis model. The osteoblast differentiation and osteogenesis-related molecules and serum bone resorption markers were measured by biochemical analysis, Alizarin Red S staining, Western blot and ELISA.
HO treatment inhibited glycolysis and osteoblast differentiation in MC3T3-E1 cells. However, when METTL14 was overexpressed, these changes induced by HO could be mitigated. Our findings indicate that METTL14 promotes GLUT3 expression via YTHDF1, leading to the modulation of various parameters in the HO-induced model. Similar positive effects of METTL14 on osteogenesis were observed in an ovariectomized mouse osteoporosis model.
METTL14 could serve as a potential therapeutic approach for enhancing osteoporosis treatment.
骨重塑失衡会导致骨质疏松症。尽管目前的药物可增强成骨细胞参与骨形成，但潜在途径仍不清楚。本研究旨在探索成骨细胞参与骨形成的途径，我们研究糖酵解和N6-甲基腺苷甲基化（m6A）对氧化应激诱导的MC3T3-E1细胞成骨损伤的保护作用。
我们使用浓度为200μM的过氧化氢（HO）建立MC3T3-E1细胞的氧化损伤模型。随后，我们检测了m6A甲基转移酶（METTL3、METTL14）、葡萄糖转运蛋白（GLUT1、GLUT3）的变化，并在体外和骨质疏松模型中验证了m6A甲基转移酶的过表达。通过生化分析、茜素红S染色、蛋白质印迹法和酶联免疫吸附测定法测量成骨细胞分化和成骨相关分子以及血清骨吸收标志物。
HO处理抑制了MC3T3-E1细胞中的糖酵解和成骨细胞分化。然而，当METTL14过表达时，HO诱导的这些变化可以得到缓解。我们的研究结果表明，METTL14通过YTHDF1促进GLUT3表达，从而调节HO诱导模型中的各种参数。在去卵巢小鼠骨质疏松模型中也观察到METTL14对成骨有类似的积极作用。
METTL14可作为增强骨质疏松症治疗的一种潜在治疗方法。
