Glucose metabolism is fundamental for the functions of all tissues, including cartilage. Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development, little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis. We show here that genetic deletion of the glucose transporter Glut1 in postnatal cartilage impairs cell proliferation and matrix production in growth plate (GPs) but paradoxically increases cartilage remnants in the metaphysis, resulting in shortening of long bones. On the other hand, articular cartilage (AC) with Glut1 deficiency presents diminished cellularity and loss of proteoglycans, which ultimately progress to cartilage fibrosis. Moreover, predisposition to Glut1 deficiency severely exacerbates injury-induced osteoarthritis. Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions, both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability. However, uncontrolled glutamine flux causes collagen overmodification, thus affecting extracellular matrix remodeling in both cartilage compartments. These results uncover the pivotal and distinct roles of Glut1-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism.

葡萄糖代谢是所有组织（包括软骨）功能的基础。尽管出现了与葡萄糖代谢在产前软骨发育调节中相关的证据，但人们对葡萄糖代谢及其生化基础在产后软骨生长和体内平衡中的作用知之甚少。我们在此表明​​，出生后软骨中葡萄糖转运蛋白 Glut1 的遗传缺失会损害生长板 (GP) 中的细胞增殖和基质产生，但矛盾的是会增加干骺端的软骨残余，导致长骨缩短。另一方面，具有 Glut1 缺陷的关节软骨 (AC) 表现出细胞结构减少和蛋白多糖丢失，最终发展为软骨纤维化。而且，Glut1 缺陷的易感性严重加剧了损伤引起的骨关节炎。无论正常情况下 GP 和 AC 软骨细胞之间葡萄糖代谢的差异如何，两种类型的软骨细胞都表现出代谢可塑性，可以在没有葡萄糖可用性的情况下增强谷氨酰胺的利用和氧化。然而，不受控制的谷氨酰胺流量会导致胶原蛋白过度修饰，从而影响两个软骨隔室中的细胞外基质重塑。这些结果揭示了 Glut1 介导的葡萄糖代谢在两个出生后软骨隔室中的关键和独特作用，并将一些软骨异常与葡萄糖/谷氨酰胺代谢改变联系起来。两种类型的软骨细胞都表现出代谢可塑性，可以在缺乏葡萄糖的情况下增强谷氨酰胺的利用和氧化。然而，不受控制的谷氨酰胺流量会导致胶原蛋白过度修饰，从而影响两个软骨隔室中的细胞外基质重塑。这些结果揭示了 Glut1 介导的葡萄糖代谢在两个出生后软骨隔室中的关键和独特作用，并将一些软骨异常与葡萄糖/谷氨酰胺代谢改变联系起来。两种类型的软骨细胞都表现出代谢可塑性，可以在缺乏葡萄糖的情况下增强谷氨酰胺的利用和氧化。然而，不受控制的谷氨酰胺流量会导致胶原蛋白过度修饰，从而影响两个软骨隔室中的细胞外基质重塑。这些结果揭示了 Glut1 介导的葡萄糖代谢在两个出生后软骨隔室中的关键和独特作用，并将一些软骨异常与葡萄糖/谷氨酰胺代谢改变联系起来。