Sirtuin 3-activated superoxide dismutase 2 mediates fluoride-induced osteoblastic differentiation in vitro and in vivo by down-regulating reactive oxygen species

IF 4.8 2区医学 Q1 TOXICOLOGY

Archives of Toxicology Pub Date : 2024-07-16 DOI:10.1007/s00204-024-03819-x

Liu Yang, Qiao Li, Sa Wang, Yi Ji, Xinbo Ma, Ming Qin, Yanhui Gao, Yanmei Yang

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Abstract

Skeletal fluorosis is a chronic metabolic bone disease caused by long-term excessive fluoride intake. Abnormal differentiation of osteoblasts plays an important role in disease progression. Research on the mechanism of fluoride-mediated bone differentiation is necessary for the prevention and treatment of skeletal fluorosis. In the present study, a rat model of fluorosis was established by exposing it to drinking water containing 50 mg/L F⁻. We found that fluoride promoted Runt-related transcription factor 2 (RUNX2) as well as superoxide dismutase 2 (SOD2) and sirtuin 3 (SIRT3) expression in osteoblasts of rat bone tissue. In vitro, we also found that 4 mg/L sodium fluoride promoted osteogenesis-related indicators as well as SOD2 and SIRT3 expression in MG-63 and Saos-2 cells. In addition, we unexpectedly discovered that fluoride suppressed the levels of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS) in osteoblasts. When SOD2 or SIRT3 was inhibited in MG-63 cells, fluoride-decreased ROS and mtROS were alleviated, which in turn inhibited fluoride-promoted osteogenic differentiation. In conclusion, our results suggest that SIRT3/SOD2 mediates fluoride-promoted osteoblastic differentiation by down-regulating reactive oxygen species.

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Sirtuin 3激活的超氧化物歧化酶2通过下调活性氧介导氟化物诱导的体外和体内成骨细胞分化。

氟骨症是一种慢性代谢性骨病，由长期过量摄入氟引起。成骨细胞的异常分化在疾病进展中起着重要作用。研究氟介导骨分化的机制对于预防和治疗骨骼氟中毒非常必要。本研究通过将大鼠暴露于含 50 mg/L 氟的饮用水中，建立了氟中毒大鼠模型。我们发现氟促进了大鼠骨组织成骨细胞中 Runt 相关转录因子 2（RUNX2）以及超氧化物歧化酶 2（SOD2）和 sirtuin 3（SIRT3）的表达。在体外，我们还发现 4 毫克/升的氟化钠能促进成骨相关指标以及 SOD2 和 SIRT3 在 MG-63 和 Saos-2 细胞中的表达。此外，我们还意外地发现氟抑制了成骨细胞中活性氧（ROS）和线粒体活性氧（mtROS）的水平。当抑制 MG-63 细胞中的 SOD2 或 SIRT3 时，氟减少的 ROS 和 mtROS 得到缓解，这反过来又抑制了氟促进的成骨分化。总之，我们的研究结果表明，SIRT3/SOD2 通过下调活性氧介导氟化物促进的成骨细胞分化。

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来源期刊

Archives of Toxicology 医学-毒理学

CiteScore

11.60

自引率

4.90%

发文量

218

审稿时长

1.5 months

期刊介绍： Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.