Tulane School of Medicine, Department of Surgery, New Orleans, 70112, United States.
Louisiana State University Health Sciences Center, Department of Orthopedics, New Orleans, LA, United States.
Sci Rep. 2019 Nov 11;9(1):16491. doi: 10.1038/s41598-019-52921-z.
The mitochondrial deacetylase sirtuin 3 (SIRT3) is thought to be one of the main contributors to metabolic flexibility-promoting mitochondrial energy production and maintaining homeostasis. In bone, metabolic profiles are tightly regulated and the loss of SIRT3 has deleterious effects on bone volume in vivo and on osteoblast differentiation in vitro. Despite the prominent role of this protein in bone stem cell proliferation, metabolic activity, and differentiation, the importance of SIRT3 for regeneration after bone injury has never been reported. We show here, using the mouse digit amputation model, that SIRT3 deficiency has no impact on the regenerative capacity and architecture of bone and soft tissue. Regeneration occurs in SIRT3 deficient mice in spite of the reduced oxidative metabolic profile of the periosteal cells. These data suggest that bone regeneration, in contrast to homeostatic bone turnover, is not reliant upon active SIRT3, and our results highlight the need to examine known roles of SIRT3 in the context of injury.
线粒体去乙酰化酶 SIRT3 被认为是促进代谢灵活性的主要贡献者之一，它可以促进线粒体能量产生和维持体内平衡。在骨骼中，代谢谱受到严格的调节，SIRT3 的缺失对体内骨量和体外成骨细胞分化有不良影响。尽管该蛋白在骨干细胞增殖、代谢活性和分化中起着重要作用，但 SIRT3 对骨损伤后的再生的重要性从未被报道过。在这里，我们使用小鼠趾断模型表明，SIRT3 缺乏对骨和软组织的再生能力和结构没有影响。尽管骨膜细胞的氧化代谢谱降低，但 SIRT3 缺乏的小鼠仍能进行再生。这些数据表明，与骨稳态更新相反，骨再生不依赖于活性 SIRT3，我们的结果强调了需要在损伤背景下检查 SIRT3 的已知作用。
