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Research Paper|Volume 13, Issue 4|pp 5150—5163

Nampt promotes osteogenic differentiation and lipopolysaccharide-induced interleukin-6 secretion in osteoblastic MC3T3-E1 cells

Shan He1,2, Hanxiang Zhang3, Yang Lu1, Zhaosi Zhang4, Xiang Zhang5, Nian Zhou1, Zhenming Hu1
  • 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • 2School of Nursing, Chongqing Medical University, Chongqing 400016, China
  • 3Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China
  • 4Department of Cerebrovascular Diseases, the First Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China
  • 5Department of Orthopaedics, Hunan Province People’s Hospital, Changsha 410005, China
Received: May 8, 2020Accepted: November 23, 2020Published: February 1, 2021
https://doi.org/10.18632/aging.202434

Copyright: © 2021 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The Nicotinamide phosphoribosyltransferase (Nampt)-NAD-Sirt1 pathway modulates processes involved in the pathogenesis of multiple diseases by influencing inflammation. This study aimed to explore the effect of Nampt in osteogenic differentiation and inflammatory response of osteoblastic MC3T3-E1 cells. We developed an in vitro model of lipopolysaccharide (LPS)-induced inflammation and showed that Nampt and Sirt1 were significantly upregulated in LPS-treated MC3T3-E1 cells. LPS induced secretion of the proinflammatory cytokine interleukin-6 (IL-6) and attenuated osteogenic differentiation. Then we transfected cells with adenoviruses to knock down or over express Nampt. Nampt promoted the expression of IL-6, TAK1 and phospho-NF-κB p65 after LPS treatment. Overexpression of Nampt overrode the effect of LPS and rescued LPS-induced inhibition on osteogenic differentiation. FK866, a Nampt inhibitor, had the same inhibitory effect as Nampt knockdown. In addition, Sirt1 suppression by EX527 decreased IL-6 secretion and NF-κB activation without changing the level of Nampt. EX527 also decreased osteogenic differentiation. Incubation with NMN or SRT 1720 also counteract the inhibitory effect of LPS and rescued osteoblast differentiation. Therefore, we demonstrated that Nampt acted both in promoting osteoblast differentiation and in enhancing inflammatory response, mediated by Sirt1 in MC3T3-E1 cells.