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烟酰胺通过激活线粒体抗氧化防御系统增强成骨细胞分化。

Nicotinamide enhances osteoblast differentiation through activation of the mitochondrial antioxidant defense system.

机构信息

Department of Molecular Genetics & Dental Pharmacology, School of Dentistry and Dental Research Institute, Dental Multi-omics Center, Seoul National University, Seoul, 08826, South Korea.

Department of Periodontology, School of Dentistry and Dental Research Institute, Seoul National University and Seoul National University Dental Hospital, Seoul, 03080, South Korea.

出版信息

Exp Mol Med. 2023 Jul;55(7):1531-1543. doi: 10.1038/s12276-023-01041-w. Epub 2023 Jul 18.

DOI:10.1038/s12276-023-01041-w
PMID:37464093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10393969/
Abstract

Although the normal physiological level of oxidative stress is beneficial for maintaining bone homeostasis, imbalance between reactive oxygen species (ROS) production and antioxidant defense can cause various bone diseases. The purpose of this study was to determine whether nicotinamide (NAM), an NAD precursor, can support the maintenance of bone homeostasis by regulating osteoblasts. Here, we found that NAM enhances osteoblast differentiation and mitochondrial metabolism. NAM increases the expression of antioxidant enzymes, which is due to increased FOXO3A transcriptional activity via SIRT3 activation. NAM has not only a preventive effect against weak and chronic oxidative stress but also a therapeutic effect against strong and acute exposure to HO in osteoblast differentiation. Collectively, the results indicate that NAM increases mitochondrial biogenesis and antioxidant enzyme expression through activation of the SIRT3-FOXO3A axis, which consequently enhances osteoblast differentiation. These results suggest that NAM could be a potential preventive or therapeutic agent for bone diseases caused by ROS.

摘要

虽然正常生理水平的氧化应激有利于维持骨稳态，但活性氧（ROS）产生和抗氧化防御之间的失衡会导致各种骨疾病。本研究旨在确定烟酰胺（NAM），一种 NAD 前体，是否可以通过调节成骨细胞来维持骨稳态。在这里，我们发现 NAM 可增强成骨细胞分化和线粒体代谢。NAM 增加抗氧化酶的表达，这是由于 SIRT3 激活增加 FOXO3A 的转录活性所致。NAM 不仅对弱而慢性的氧化应激具有预防作用，而且对成骨细胞分化中强而急性的 HO 暴露也具有治疗作用。总之，这些结果表明，NAM 通过激活 SIRT3-FOXO3A 轴增加线粒体生物发生和抗氧化酶的表达，从而增强成骨细胞分化。这些结果表明，NAM 可能是治疗由 ROS 引起的骨疾病的潜在预防或治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/75c06a320a0c/12276_2023_1041_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/54345f8f7793/12276_2023_1041_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/05927c5c567e/12276_2023_1041_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/b7355d858daa/12276_2023_1041_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/2b0715a00f6c/12276_2023_1041_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/cbcce5128d17/12276_2023_1041_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/75c06a320a0c/12276_2023_1041_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/54345f8f7793/12276_2023_1041_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/05927c5c567e/12276_2023_1041_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/b7355d858daa/12276_2023_1041_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/2b0715a00f6c/12276_2023_1041_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/cbcce5128d17/12276_2023_1041_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e492/10393969/75c06a320a0c/12276_2023_1041_Fig6_HTML.jpg

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