Deng Jie, Zeng Xiaoxiao, Zhang Kailin, Zhang Ting, Dong Yangting, Zou Jian, Wu Changxue, Li Yi, Li Fucheng, Guan Zhizhong
Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China.
Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China.
Biol Trace Elem Res. 2025 Apr;203(4):2013-2028. doi: 10.1007/s12011-024-04327-w. Epub 2024 Aug 6.
This study aimed to explore the role of histone methyltransferase SET and MYND domain containing 3 (SMYD3) in bone metabolism of osteoblasts exposed to fluoride. The levels of urine fluoride, BALP, and OC and the mRNA expression of SMYD3 were determined in patients with skeletal fluorosis and non-fluoride-exposed people on informed consent. The expression of SMYD3 protein, OC contents, and BALP activities were detected in human osteoblast-like MG63 cells and rat primary osteoblasts treated with sodium fluoride (NaF) for 48 h. The autophagosomes were observed by transmission electron microscopy. Then, we knocked down SMYD3 to confirm whether it was involved in the regulation of bone formation and related to autophagy and Wnt/β-catenin pathway. We observed that OC and BALP levels in patients with skeletal fluorosis significantly increased, while the mRNA expression of SMYD3 significantly decreased in the skeletal fluorosis groups. In vitro, the OC contents, BALP activities, and expression of SMYD3 significantly increased, and many autophagosomes were observed in NaF treated osteoblasts. The downregulation of SMYD3 significantly inhibited OC contents, BALP activities, and expression of autophagy-related proteins, but with no significant changes in the Wnt/β-catenin pathway. Our results demonstrated that fluoride exposure with coal-burning pollution caused orthopedic injuries and abnormalities in the levels of OC and BALP and hindered normal bone metabolism. Silencing the SMYD3 gene could significantly reduce OC and BALP levels via inhibiting the increase in autophagy induced by fluoride.
本研究旨在探讨组蛋白甲基转移酶含SET和MYND结构域3（SMYD3）在暴露于氟的成骨细胞骨代谢中的作用。在获得知情同意的情况下，测定了氟骨症患者和未接触氟的人群的尿氟、骨碱性磷酸酶（BALP）和骨钙素（OC）水平以及SMYD3的mRNA表达。检测了用氟化钠（NaF）处理48小时的人成骨样MG63细胞和大鼠原代成骨细胞中SMYD3蛋白的表达、OC含量和BALP活性。通过透射电子显微镜观察自噬体。然后，我们敲低SMYD3以确认其是否参与骨形成的调节以及是否与自噬和Wnt/β-连环蛋白通路相关。我们观察到，氟骨症患者的OC和BALP水平显著升高，而氟骨症组中SMYD3的mRNA表达显著降低。在体外，NaF处理的成骨细胞中OC含量、BALP活性和SMYD3的表达显著增加，并且观察到许多自噬体。SMYD3的下调显著抑制了OC含量、BALP活性和自噬相关蛋白的表达，但Wnt/β-连环蛋白通路无显著变化。我们的结果表明，燃煤污染导致的氟暴露引起了骨科损伤以及OC和BALP水平异常，并阻碍了正常的骨代谢。沉默SMYD3基因可通过抑制氟诱导的自噬增加显著降低OC和BALP水平。
