Niacin regulates glucose metabolism and osteogenic differentiation via the SIRT2-C/EBPβ-AREG signaling axis

• Published in: Biomedicine & pharmacotherapy 2024-11, Vol.180, p.117447, Article 117447
• Main Authors: Ma, Jinlong, Li, Xiang, Li, Qiuyue, Sun, Zhenqian, You, Yunhao, Zhang, Lu, Ji, Zhongjie, Zhou, Hongming, Zhang, Qingju, Wang, Limin, Wang, Hongliang, Jiao, Guangjun, Chen, Yunzhen
• Format: Article
• Language: English
• Subjects: Animals; AREG; CCAAT-Enhancer-Binding Protein-beta - metabolism; Cell Differentiation - drug effects; Glucose - metabolism; Humans; Male; Mice; Mice, Inbred C57BL; Niacin; Niacin - pharmacology; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteogenesis - drug effects; Osteogenic differentiation; Osteoporosis; Osteoporosis - metabolism; Osteoporosis - pathology; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Sirtuin 2 - genetics; Sirtuin 2 - metabolism
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117447

The pathogenesis of osteoporosis is driven by several mechanisms including the imbalance between osteoblastic bone formation and osteoclastic bone resorption. Currently, the role of Niacin (NA), also known as vitamin B3, in the regulation of osteoblastic differentiation is not fully understood. Data from the NHANES database were employed to investigate the association of NA intake with the prevalence of osteoporosis. Alterations in mRNA and protein levels of genes and proteins involved in osteogenic differentiation were evaluated via techniques including qRT-PCR, protein immunoblotting, Alkaline Phosphatase (ALP) activity analysis, ALP staining, and Alizarin Red staining. Changes in the mouse skeletal system were investigated by organizational analysis and Micro-CT. The results indicated that NA promoted osteogenic differentiation. Co-immunoprecipitation and chromatin immunoprecipitation were performed to explore the underlying mechanisms. It was observed that NA promoted AREG expression by deacetylating C/EBPβ via SIRT2, thereby activating the PI3K-AKT signaling pathway. It also enhanced the activity of the pivotal glycolytic enzyme, PFKFB3. This cascade amplified osteoblast glycolysis, facilitating osteoblast differentiation. These findings demonstrate that NA modulates glucose metabolism and influences osteogenic differentiation via the SIRT2-C/EBPβ-AREG pathway, suggesting that NA may be a potential therapeutic agent for the management of osteoporosis, and AREG could be a plausible target. •The intake of niacin is significantly lower in patients with osteoporosis.•Niacin promotes glucose metabolism and osteogenic process.•Niacin activates the PI3K/AKT signalling pathway via AREG.•SIRT2 enhances C/EBPβ transcriptional activity through deacetylation.