Department of Orthopedics, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Baiyun District, Guangzhou, Guangdong, 510515, China.
Orthopaedic Department, The 4th medical center of Chinese PLA General Hospital, Beijing, 100089, China.
Cell Mol Life Sci. 2024 Jun 15;81(1):260. doi: 10.1007/s00018-024-05297-x.
The pathological advancement of osteoporosis is caused by the uneven development of bone marrow-derived mesenchymal stem cells (BMSCs) in terms of osteogenesis and adipogenesis. While the role of EEF1B2 in intellectual disability and tumorigenesis is well established, its function in the bone-fat switch of BMSCs is still largely unexplored. During the process of osteogenic differentiation, we observed an increase in the expression of EEF1B2, while a decrease in its expression was noted during adipogenesis. Suppression of EEF1B2 hindered the process of osteogenic differentiation and mineralization while promoting adipogenic differentiation. On the contrary, overexpression of EEF1B2 enhanced osteogenesis and strongly inhibited adipogenesis. Furthermore, the excessive expression of EEF1B2 in the tibias has the potential to mitigate bone loss and decrease marrow adiposity in mice with osteoporosis. In terms of mechanism, the suppression of β-catenin activity occurred when EEF1B2 function was suppressed during osteogenesis. Our collective findings indicate that EEF1B2 functions as a regulator, influencing the differentiation of BMSCs and maintaining a balance between bone and fat. Our finding highlights its potential as a therapeutic target for diseases related to bone metabolism.
骨质疏松症的病理进展是由于骨髓间充质干细胞（BMSCs）在成骨和脂肪生成方面的不均匀发育所致。虽然 EEF1B2 在智力残疾和肿瘤发生中的作用已得到充分证实，但它在 BMSCs 的骨脂肪转换中的功能在很大程度上仍未得到探索。在成骨分化过程中，我们观察到 EEF1B2 的表达增加，而在脂肪生成过程中则观察到其表达减少。抑制 EEF1B2 会阻碍成骨分化和矿化过程，同时促进脂肪生成分化。相反，EEF1B2 的过表达增强了成骨作用，并强烈抑制了脂肪生成。此外，在骨质疏松症小鼠的胫骨中过度表达 EEF1B2 有减轻骨丢失和减少骨髓脂肪的潜力。就机制而言，当 EEF1B2 在成骨过程中抑制其功能时，β-连环蛋白活性受到抑制。我们的研究结果表明，EEF1B2 作为一种调节剂发挥作用，影响 BMSCs 的分化，并维持骨与脂肪之间的平衡。我们的发现强调了它作为与骨代谢相关疾病的治疗靶点的潜力。
