The involvement of nitric oxide (NO) in preventing bone loss has long been hypothesized, but despite decades of research the mechanisms remain obscure. In this issue of the JCI, Jin et al. explored NO deficiency using human cell and mouse models that lacked argininosuccinate lyase (ASL), the enzyme involved in synthesizing arginine and NO production. Osteoblasts that did not express ASL produced less NO and failed to differentiate. Notably, in the context of Asl deficiency, heterozygous deletion of caveolin 1, which normally inhibits NO synthesis, restored NO production, osteoblast differentiation, glycolysis, and bone mass. These experiments suggest that ASL regulates arginine synthesis in osteoblasts, which leads to enhanced NO production and increased glucose metabolism. After a period when research slowed, these studies, like the legendary phoenix, renew the exploration of NO in bone biology, and provide exciting translational potential.
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机译：长期以来，人们一直假设一氧化氮 （NO） 参与预防骨质流失，但尽管进行了数十年的研究，其机制仍然不清楚。在本期 JCI 中，Jin 等人使用缺乏精氨酸琥珀酸裂解酶 （ASL） 的人类细胞和小鼠模型探讨了 NO 缺乏症，ASL 是参与合成精氨酸和 NO 产生的酶。不表达 ASL 的成骨细胞产生较少的 NO 且无法分化。值得注意的是，在 Asl 缺陷的情况下，通常抑制 NO 合成的小窝蛋白 1 杂合缺失恢复了 NO 的产生、成骨细胞分化、糖酵解和骨量。这些实验表明，ASL 调节成骨细胞中精氨酸的合成，从而导致 NO 产生增加和葡萄糖代谢增加。在研究放缓的时期之后，这些研究就像传说中的凤凰一样，重新探索了骨生物学中 NO 的探索，并提供了令人兴奋的转化潜力。
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