SIRT6 regulates osteogenic differentiation of rat bone marrow mesenchymal stem cells partially via suppressing the nuclear factor-κB signaling pathway

Stem Cells. 2014 Jul;32(7):1943-55. doi: 10.1002/stem.1671.


Sirtuin 6 (SIRT6) is a NAD-dependent deacetylase involved in lifespan regulation. To evaluate the effect of SIRT6 on osteogenesis, rat bone marrow mesenchymal stem cells (rBMSCs) with enhanced or reduced SIRT6 function were developed. We observed that SIRT6 knockdown significantly reduced the mRNA levels of several key osteogenic markers in vitro, including alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin, while overexpression of SIRT6 enhanced their expression. Additionally, SIRT6 knockdown activated nuclear factor-κB (NF-κB) transcriptional activity and upregulated the expression of acetyl-NF-κB p65 (Lys310). The decreased osteogenic differentiation ability of rBMSCs could be partially rescued by the addition of NF-κB inhibitor BAY 11-7082. Furthermore, SIRT6 overexpression in rBMSCs combined with the use of collagen/chitosan/hydroxyapatite scaffold could significantly boost new bone formation in rat cranial critical-sized defects, as determined by microcomputed tomography and histological examination. These data confirm that SIRT6 is mainly located in the nuclei of rBMSCs and plays an essential role in their normal osteogenic differentiation, partly by suppressing NF-κB signaling.

Keywords: BMSCs; Bone regeneration; Calvarial defects; Collagen/chitosan/HA scaffolds; Nuclear factor-κB; SIRT6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Regeneration
  • Cell Adhesion
  • Cell Differentiation*
  • Cell Nucleus / enzymology
  • Cell Proliferation
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Gene Expression
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / physiology*
  • NF-kappa B / metabolism*
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Sirtuins / physiology*


  • Core Binding Factor Alpha 1 Subunit
  • NF-kappa B
  • Runx2 protein, rat
  • Osteocalcin
  • Alkaline Phosphatase
  • Sirtuins
  • sirtuin 6, rat