Institute of Laboratory Animal Science, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Institute of Laboratory Animal Science, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Biomed Pharmacother. 2021 May;137:111380. doi: 10.1016/j.biopha.2021.111380. Epub 2021 Feb 15.
Iron is an essential trace element in the metabolism of almost all living organisms. Iron overload can disrupt bone homeostasis by significant inhibition of osteogenic differentiation and stimulation of osteoclastogenesis, consequently leading to osteoporosis. Iron accumulation is also involved in the osteoporosis induced by multiple factors, such as estrogen deficiency, ionizing radiation, and mechanical unloading. Iron chelators are first developed for treating iron overloaded disorders. However, growing evidence suggests that iron chelators can be potentially used for the treatment of bone loss. In this review, we focus on the therapeutic effects of iron chelators on bone loss. Iron chelators have therapeutic effects not only on iron overload induced osteoporosis, but also on osteoporosis induced by estrogen deficiency, ionizing radiation, and mechanical unloading, and in Alzheimer's disease-associated osteoporotic deficits. Iron chelators differently affect the cellular behaviors of bone cells. For osteoblast lineage cells (bone mesenchymal stem cells and osteoblasts), iron chelation stimulates osteogenic differentiation. Conversely, iron chelation significantly inhibits osteoclast differentiation. These different responses may be associated with the different needs of iron during differentiation. Fibroblast growth factor 23, angiogenesis, and antioxidant capability are also involved in the osteoprotective effects of iron chelators.
铁是几乎所有生物体代谢所必需的微量元素。铁过载可通过显著抑制成骨分化和刺激破骨细胞生成，从而导致骨质疏松。铁积累也参与了由多种因素引起的骨质疏松症，如雌激素缺乏、电离辐射和机械去负荷。铁螯合剂最初是为治疗铁过载疾病而开发的。然而，越来越多的证据表明，铁螯合剂可能可用于治疗骨丢失。在这篇综述中，我们重点关注铁螯合剂对骨丢失的治疗作用。铁螯合剂不仅对铁过载诱导的骨质疏松症有治疗作用，而且对雌激素缺乏、电离辐射和机械去负荷以及阿尔茨海默病相关骨质疏松症也有治疗作用。铁螯合剂对成骨细胞系细胞（骨间充质干细胞和成骨细胞）的细胞行为有不同的影响。铁螯合刺激成骨分化。相反，铁螯合显著抑制破骨细胞分化。这些不同的反应可能与分化过程中对铁的不同需求有关。成纤维细胞生长因子 23、血管生成和抗氧化能力也参与了铁螯合剂的护骨作用。
