| First Author | Qu B | Year | 2016 |
| Journal | Biochem Biophys Res Commun | Volume | 478 |
| Issue | 1 | Pages | 439-445 |
| PubMed ID | 27378422 | Mgi Jnum | J:238683 |
| Mgi Id | MGI:5823348 | Doi | 10.1016/j.bbrc.2016.06.154 |
| Citation | Qu B, et al. (2016) Sirtuin1 promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor gamma in MC3T3-E1 cells. Biochem Biophys Res Commun 478(1):439-45 |
| abstractText | Osteoporosis is a skeletal disorder characterized by bone loss, resulting in architectural deterioration of the skeleton, decreased bone strength and an increased risk of fragility fractures. Strengthening osteogenesis is an effective way to relieve osteoporosis. Sirtuin1 (Sirt1) is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, which is reported to be involved in improving osteogenesis. Sirt1 targets peroxisome proliferator-activated receptor gamma (PPARgamma) in the regulation of adipose tissues; however, the molecular mechanism of Sirt1 in osteogenic differentiation is still unknown. PPARgamma tends to induce more adipogenic differentiation rather than osteogenic differentiation. Hence, we hypothesized that Sirt1 facilitates osteogenic differentiation through downregulation of PPARgamma signaling. Mouse pre-osteoblastic MC3T3-E1 cells were cultured under osteogenic medium. Sirt1 was overexpressed through plasmid transfection. The results showed that high expression of Sirt1 was associated with increased osteogenic differentiation, as indicated by quantitative PCR and Western blot analysis of osteogenic markers, and Von Kossa staining. Sirt1 overexpression also directly and negatively regulated the expression of PPARgamma and its downstream molecules. Use of the PPARgamma agonist Rosiglitazone, reversed the effects of Sirt1 on osteogenic differentiation. Using constructed luciferase plasmids, we demonstrated a role of Sirt1 in inhibiting PPARgamma-induced activity and expression of adipocyte-specific genes, including acetyl-coenzyme A carboxylase (Acc) and fatty acid binding protein 4 (Fabp4). The interaction between Sirt1 and PPARgamma was further confirmed using co-immunoprecipitation analysis. Together, these results reveal a novel mechanism for Sirt1 in osteogenic differentiation through downregulation of PPARgamma activity. These findings suggest that the Sirt1-PPARgamma pathway may represent a potential target for enhancement of osteogenesis and treatment of osteoporosis. |
