SIRT1通过PI3K/AKT通路促进成骨细胞分化的相关机制研究

Abstract
Figure/Table
References (0)
Related Citation (0)

Download: PDF (1850 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To studying the interaction between the SIRT1 gene and the PI3K-AKT pathway and investigate the effect of SIRT1 on osteoblast differentiation. Methods Osteoblasts were extracted from the skull of Sprague Dawley rats and cultured for 3～4 passages.Then Cells were randomized into control group，resveratrol group and resveratrol + EX-527 group.Cell Counting Kit-8 (CCK-8) was used to determine the cytotoxicity of resveratrol and EX-527.Alkaline phosphatase (ALP) and alizarin red S staining were used to detect ALP levels and calcium nodules，respectively.Immunohistochemistry was used to observe the production of type I collagen to determine the differentiation of cells.The expression of SIRT1，Runt-related transcription factor 2 (RUNX2)，Osteopontin (OPN) and the phosphorylation levels of phosphatidylinositol 3 kinase(PI3K)andprotein kinaseB(AKT).Results Resveratrol and EX-527 had no effect on cell proliferation (P＞0.05).ALP level and calcium nodules increased significantly after addition of resveratrol，but decreased significantly after addition of EX-527.The amont of Type I collagen were up-regulated because of the resveratrol.The expression of RUNX2 and OPN in osteoblast increased with the increase of SIRT1 expression (P＜0.01 or P＜0.001).When SIRT1 was inhibited，the protein expression of related factors also decreased (P＜0.001).Concurrently，the phosphorylated levels of PI3K and AKT also showed SIRT1-dependent up-regulation and down-regulation (P＜0.05 or P＜0.001).Conclusion The effect of SIRT1 on rat osteoblast differentiation may be mediated through the PI3K-AKT pathway.

Key words： resveratrol Sirtuin 1 osteoblast differentiation

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

URL:

http://www.sygkzz.com/EN/ OR http://www.sygkzz.com/EN/Y2018/V24/I6/523

［1］Boyce BF，Rosenberg E，Papp AE，et al.The osteoclast，bone remodelling and treatment of metabolic bone disease［J］.Eur J Clin Invest，2012，42(12)：1332-1341.
［2］Haigis MC，Sinclair DA.Mammalian sirtuins：biological insights and disease relevance［J］.Annu Rev Pathol，2010，(1)：253-295.
［3］Baur JA，Ungvari Z，Minor RK，et al.Are sirtuins viable targets for improving healthspan and lifespan?［J］.NatRev Drug Discov，2012；11(6)：443-461.
［4］Srividhya L，Li H，Shoshana MB，et al.Sirtuin1(Sirt1)promotes cortical bone formation by preventing βCatenin sequestration by foxO transcription factors in osteoblast progenitors［J］.J Biol Chem，2014，289(35)：24069-24078.
［5］Einav CK，Hanna A，Avi L，et al.Sirt1 is a regulator of bone mass and a repressor of sost encoding for sclerostin，a bone formation inhibitor［J］.Endocrinology，2011，152(12)：4514-4524.
［6］Tokio M，Takehiko M，Koji T，et al.Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice［J］.Ann Rheum Dis，2014，73(7)：1397-1404.
［7］Jeong JK，Moon MH，Lee YJ，et al.Autophagy induced by the class Ⅲ histone deacetylase Sirt1 prevents prion peptide neurotoxicity［J］.Neurobiol Aging，2013，34(1)：146-156.
［8］Maiko S，John D，Bartlett.Sirtuin1 and autophagy protect cells from fluoride-induced cell stress［J］.Biochim Biophys Acta，2014，1842(2)：245-255.
［9］Zhang J，Kang N，Yu X，et al.Radial extracorporeal shock wave therapy enhances the proliferation and differentiation of neural stem cells by notch，PI3K/AKT，and Wnt/β-catenin signaling［J］.Sci Rep，2017，7(1)：1-10.
［10］Spassov SG，Donus R，Ihle R，et al.Corrigendum to hydrogen sulfide prevents formation of reactive Oxygen species through PI3K/Akt signaling and limits ventilator-induced lung injury［J］.Oxid Med Cell Longev，2017，2017：3715037.
［11］Wang XY，Zhang XH，Peng L，et al.Bardoxolone methyl(CDDO-Me or RTA402)induces cell cycle arrest，apoptosis and autophagy via PI3K/Akt/mTOR and p38 MAPK/Erk1/2 signaling pathways in K562 cells［J］.Am J Transl Res，2017，9(10)：4652-4672.
［12］Aarom WJ，Shen J，Zhang XL，et al.NELL-1 in the treatment of osteoporotic bone loss［J］.Nat Commun，2015，17(6)：1-14.
［13］Petra S，Kayuan Z，Eric B，et al.SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin［J］.EMBO Mol Med，2013，5(3)：430-440.
［14］Hanna A，Einav CK，Irina G，et al.The sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice［J］.Edocrinology，2014，155(9)：3508-3515.
［15］Ye E，Jiang Z，Lu X，et al.GZD824 suppresses the growth of human B cell precursor acute lymphoblastic leukemia cells by inhibiting the SRC kinase and PI3K/AKT pathways［J］.Oncotarget，2016，8(50)：87002-87015.
［16］Deng F，Ma YX，Liang L，et al.The pro-apoptosis effect of sinomenine in renal carcinoma via inducing autophagy through inactivating PI3K/AKT/mTOR pathway［J］.Biomed Pharmacother，2017(97)：1269-1274.
［17］Chen X，Bian M，Zhang C，et al.Dihydroartemisinin inhibits ER stress-mediated mitochondrial pathway to attenuate hepatocyte lipoapoptosis via blocking the activation of the PI3K/Akt pathway［J］.Biomed Pharmacother，2017(97)：975-984.