2. Academic Validation
  3. The protection of nicotinamide riboside against diabetes mellitus-induced bone loss via OXPHOS

The protection of nicotinamide riboside against diabetes mellitus-induced bone loss via OXPHOS

  • Bone. 2025 Jan 28:193:117411. doi: 10.1016/j.bone.2025.117411.
Jie Gao 1,  Xiangyuan Meng 2,  Xingxiang Yang 3,  Chenqi Xie 4,  Chunyan Tian 5,  Jianbao Gong 6,  Junwei Zhang 7,  Shiyou Dai 8,  Tianlin Gao 9
Affiliations

Affiliations

  • 1 Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266000, China; School of Public Health, Qingdao University, Qingdao 266071, China. Electronic address: gaojie2@qdu.edu.cn.
  • 2 Department of Toxicology, School of Public Health, Jilin University, Changchun 130021, China. Electronic address: xymeng23@mails.jlu.edu.cn.
  • 3 School of Public Health, Qingdao University, Qingdao 266071, China. Electronic address: yangxingxiang@qdu.edu.cn.
  • 4 School of Public Health, Qingdao University, Qingdao 266071, China. Electronic address: xiechenqi@qdu.edu.cn.
  • 5 School of Public Health, Qingdao University, Qingdao 266071, China.
  • 6 Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266000, China.
  • 7 Shandong Wendeng Osteopathic Hospital, Weihai 264400, China.
  • 8 Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266000, China. Electronic address: daishiyouhr@sina.com.
  • 9 School of Public Health, Qingdao University, Qingdao 266071, China. Electronic address: gaotl@qdu.edu.cn.
PMID: 39884488 DOI: 10.1016/j.bone.2025.117411
Abstract

Diabetes mellitus is a global disease that results in various complications, including diabetic osteoporosis. Prior studies have indicated a correlation between low levels of nicotinamide adenine dinucleotide (NAD+) and diabetes-related complications. Nicotinamide riboside (NR), a widely utilized precursor vitamin of NAD+, has been demonstrated to enhance age-related osteoporosis through the SIRT1/FOXO/β-catenin pathway in osteoblast progenitors. However, the impact of NR on bone health in diabetes mellitus remains unclear. In this study, we assessed the potential effects of NR on bone in diabetic mice. NR was administered to high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetic mice (T2DM), and various parameters, including metabolic indicators, bone quality, bone metabolic markers, and RNA sequences, were measured. Our findings confirmed that HFD/STZ-induced T2DM impaired bone microstructures, resulting in bone loss. NR effectively ameliorated Insulin resistance, improved bone microarchitecture, and bone quality, reduced bone resorption, enhanced the Forkhead box O (FOXO) signaling pathway, mitigated the nuclear factor kappa B (NF-kB) signaling pathway, and ameliorated the disorder of the Oxidative Phosphorylation process (OXPHOS) in diabetic mice. In conclusion, NR demonstrated the capacity to alleviate T2DM-induced bone loss through the modulation of OXPHOS in type 2 diabetic mice. Our results underscore the potential of NR as a therapeutic target for addressing T2DM-related bone metabolism and associated diseases. Further cell-based studies under diabetic conditions, such as in vitro cultures of key cell types (e.g., osteoblasts and osteoclasts), are necessary to validate these findings.

Keywords

Bone loss; Diabetes mellitus; NAD(+); NR; OXPHOS.

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