Department of Internal Medicine 3, Friedrich Alexander University of Erlangen-Nuremberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Sci Rep. 2020 Dec 3;10(1):21020. doi: 10.1038/s41598-020-77892-4.
Osteoclasts are specialised bone resorbing cells that control both physiological and pathological bone turnover. Functional changes in the differentiation and activity of osteoclasts are accompanied by active metabolic reprogramming. However, the biological significance and the in vivo relevance of these events has remained unclear. Here we show that bone resorption of differentiated osteoclasts heavily relies on increased aerobic glycolysis and glycolysis-derived lactate production. While pharmacological inhibition of glycolysis did not affect osteoclast differentiation or viability, it efficiently blocked bone resorption in vitro and in vivo and consequently ameliorated ovariectomy-induced bone loss. Our experiments thus highlight the therapeutic potential of interfering with osteoclast-intrinsic metabolic pathways as possible strategy for the treatment of diseases characterized by accelerated bone loss.
破骨细胞是专门的骨吸收细胞，可控制生理和病理骨质转换。破骨细胞的分化和活性的功能变化伴随着活跃的代谢重编程。然而，这些事件的生物学意义和体内相关性仍不清楚。在这里，我们表明，分化的破骨细胞的骨吸收严重依赖于有氧糖酵解和糖酵解衍生的乳酸产生的增加。虽然糖酵解的药理学抑制作用不影响破骨细胞的分化或活力，但它有效地阻断了体外和体内的骨吸收，从而改善了卵巢切除诱导的骨丢失。因此，我们的实验强调了干扰破骨细胞内在代谢途径的治疗潜力，作为治疗以加速骨丢失为特征的疾病的可能策略。
