The metabolic program of osteoblasts, the chief bone-making cells, remains incompletely understood. Here in murine calvarial cells, we establish that osteoblast differentiation under aerobic conditions is coupled with a marked increase in glucose consumption and lactate production but reduced oxygen consumption. As a result, aerobic glycolysis accounts for approximately 80% of the ATP production in mature osteoblasts. In vivo tracing with ¹³C-labeled glucose in the mouse shows that glucose in bone is readily metabolized to lactate but not organic acids in the TCA cycle. Glucose tracing in osteoblast cultures reveals that pyruvate is carboxylated to form malate integral to the malate-aspartate shuttle. RNA sequencing (RNA-seq) identifies Me2, encoding the mitochondrial NAD-dependent isoform of malic enzyme, as being specifically upregulated during osteoblast differentiation. Knockdown of Me2 markedly reduces the glycolytic flux and impairs osteoblast proliferation and differentiation. Thus, the mitochondrial malic enzyme functionally couples the mitochondria with aerobic glycolysis in osteoblasts.

成骨细胞（主要的造骨细胞）的代谢程序仍未完全了解。在这里，在鼠颅盖细胞中，我们确定有氧条件下的成骨细胞分化与葡萄糖消耗和乳酸产生的显着增加相结合，但氧消耗减少。结果，有氧糖酵解约占成熟成骨细胞中ATP产量的80％。在小鼠体内用¹³ C标记的葡萄糖进行的体内追踪显示，在TCA循环中，骨骼中的葡萄糖易于代谢为乳酸，而不能代谢为有机酸。成骨细胞培养物中的葡萄糖示踪显示丙酮酸被羧化形成苹果酸-天冬氨酸穿梭的不可或缺的苹果酸。RNA测序（RNA-seq）识别Me2，编码苹果酸酶的线粒体NAD依赖性亚型，在成骨细胞分化过程中被特异性上调。抑制Me2会显着降低糖酵解通量并损害成骨细胞的增殖和分化。因此，线粒体苹果酸酶功能性地将线粒体与成骨细胞中的需氧糖酵解耦合。