组蛋白去乙酰化酶Sirtuin 1在糖尿病和骨代谢中的研究进展
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摘要
组蛋白去乙酰化酶Sirtuin 1是第Ⅲ类去乙酰化酶,在糖尿病和骨代谢中起重要作用。Sirtuin 1对糖尿病的影响较明确,是胰岛β细胞的保护性因子,促进胰岛素分泌,增加糖异生,减少氧化应激,改善肝脏、脂肪和骨骼肌的IR。Sirtuin1可促进成骨细胞分化,抑制破骨细胞生成,调节骨重建,还同时影响糖尿病和骨代谢。但是,Sirtuin 1在糖尿病合并骨代谢异常方面的研究正处于开始阶段,多集中在细胞水平的表观遗传学领域。本文就Sirtuin 1在糖尿病和骨代谢中的作用及相关信号转导机制的研究进展进行综述,为糖尿病性骨质疏松症的防治提供新思路。
The third class of histone deacetylase,Sirtuin 1,have an important role both in diabetes and bone metabolism. The effects of Sirtuin 1 on diabetes were clear. It is a protective factor for the pancre-atic β-cell and promotes insulin secretion and gluconeogenesis. Meanwhile,Sirtuin 1 can attenuate the oxida-tive damage and the insulin resistance(IR)of the liver,skeletal muscle and adipose tissue. Additionaly,it is proved that Sirtuin 1 regulates bone remodeling by increasing osteoblastogenesis and decreasing osteoclasto-genesis. However,there are few researches on the influence of Sirtuin 1 on diabetic osteoporosis. Some re-ports in cell experiments and epigenetics. Here,we summarized the role of Sirtuin 1 in diabetes,bone metab-olism and associated signal pathway to explore the underlying mechanisms,and provided new approaches for the prevention and treatment of diabetic osteoporosis.
The third class of histone deacetylase,Sirtuin 1,have an important role both in diabetes and bone metabolism. The effects of Sirtuin 1 on diabetes were clear. It is a protective factor for the pancre-atic β-cell and promotes insulin secretion and gluconeogenesis. Meanwhile,Sirtuin 1 can attenuate the oxida-tive damage and the insulin resistance(IR)of the liver,skeletal muscle and adipose tissue. Additionaly,it is proved that Sirtuin 1 regulates bone remodeling by increasing osteoblastogenesis and decreasing osteoclasto-genesis. However,there are few researches on the influence of Sirtuin 1 on diabetic osteoporosis. Some re-ports in cell experiments and epigenetics. Here,we summarized the role of Sirtuin 1 in diabetes,bone metab-olism and associated signal pathway to explore the underlying mechanisms,and provided new approaches for the prevention and treatment of diabetic osteoporosis.
引文
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[7] Feng J,Liu S,Ma S,et al. Protective effects of resveratrol on postmenopausal osteoporosis:regulation of SIRT1NFkappaB signaling pathway. Acta Biochim Biophys Sin(Shanghai),2014,46:10241033.
[8] Xu C,Cai Y,Fan P,et al. Calorie restriction prevents metabolic aging caused by abnormal SIRT1 function in adipose tissues.Diabetes,2015,64:15761590.
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[10]He X,Andersson G,Lindgren U,et al. Resveratrol prevents RANKLinduced osteoclast differentiation of murine osteoclast progenitor RAW 264. 7 cells through inhibition of ROS production. Biochem Biophys Res Commun,2010,401:356362.
[11]Zheng W,Feng Z,You S,et al. Fisetin inhibits IL1betainduced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. Int Immunopharmacol,2017,45:135147.
[12]Zhou Y,Song T,Peng J,et al. SIRT1 suppresses adipogenesis by activating Wnt/betacatenin signaling in vivo and in vitro. Oncotarget,2016,7:7770777720.
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[15]Prud'homme GJ,Glinka Y,Udovyk O,et al. GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity. Biochem Biophys Res Commun,2014,452:649654.
[16]Chen YR,Lai YL,Lin SD,et al. SIRT1 interacts with metabolic transcriptional factors in the pancreas of insulinresistant and calorierestricted rats. Mol Biol Rep,2013,40:33733380.
[17]Bordone L,Motta MC,Picard F,et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreaticβcells. PLoS Biol,2006,4:e31.
[18]Jia L,Li W,Li J,et al. Lycium barbarum polysaccharide attenuates highfat dietinduced hepatic steatosis by upregulating SIRT1 expression and deacetylase activity. Sci Rep,2016,6:36209.
[19]Xu L,Kanasaki M,He J,et al. Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagyassociated molecules. Biochim Biophys Acta,2013,1832:16051612.
[20]Valdecantos MP,PerezMatute P,GonzalezMuniesa P,et al.Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. Obesity,2012,20:19741983.
[21]Liu J,Han W,Chen L,et al. Mechanism of osteogenic and adipogenic differentiation of tendon stem cells induced by sirtuin 1.Mol Med Rep,2016,14:16431648.
[22]Zhou X,Wang F,Yang H,et al. Seleniumenriched exopolysaccharides produced by Enterobacter cloacae Z0206 alleviate adipose inflammation in diabetic KKAy mice through the AMPK/SirT1 pathway. Mol Med Rep,2014,9:683688.
[23]Wende AR,Huss JM,Schaeffer PJ,et al. PGC1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha:a mechanism for transcriptional control of muscle glucose metabolism. Mol Cell Biol,2005,25:1068410694.
[24]Wu Z,Puigserver P,Andersson U,et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC1. Cell,1999,98:115124.
[25]Frojdo S,Durand C,Molin L,et al. Phosphoinositide 3kinase as a novel functional target for the regulation of the insulin signaling pathway by SIRT1. Mol Cell Endocrinol,2011,335:166176.
[26]Crandall JP,Oram V,Trandafirescu G,et al. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci,2012,67:13071312.
[27]JimenezGomez Y,Mattison JA,Pearson KJ,et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on highfat,highsugar diet. Cell Metab,2013,18:533545.
[28]Cao Y,Jiang X,Ma H,et al. SIRT1 and insulin resistance. J Diabetes Complications,2016,30:178183.
[29]GodfrinValnet M,Khan KA,Guillot X,et al. Sirtuin 1 activity in peripheral blood mononuclear cells of patients with osteoporosis. Med Sci Monit Basic Res,2014,20:142145.
[30]Hong W,Xu XY,Qiu ZH,et al. Sirt1 is involved in decreased bone formation in aged apolipoprotein Edeficient mice. Acta Pharmacol Sin,2015,36:14871496.
[31]Gurt I,Artsi H,CohenKfir E,et al. The sirt1 activators SRT2183 and SRT3025 inhibit ranklinduced osteoclastogenesis in bone marrowderived macrophages and downregulate Sirt3 in Sirt1 null cells. PloS one,2015,10:e0134391.
[32]Tseng PC,Hou SM,Chen RJ,et al. Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis. J Bone Miner Res,2011,26:25522563.
[33]Kim HN,Han L,Iyer S,et al. Sirtuin1 suppresses osteoclastogenesis by deacetylating FoxOs. Mol Endocrinol,2015,29:14981509.
[34]Li Y,Shen G,Yu C,et al. Angiotensin II induces mitochondrial oxidative stress and mtDNA damage in osteoblasts by inhibiting SIRT1–FoxO3a–MnSOD pathway. Biochem Biophys Res Commun,2014,455:113118.
[35]Backesjo CM,Li Y,Lindgren U,et al. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. Cells Tissues Organs,2009,189:9397.
[36]Kobayashi Y,Uehara S,Udagawa N,et al. Regulation of bone metabolism by Wnt signals. J Biochem,2016,159:387392.
[37]Feng G,Zheng K,Song D,et al. SIRT1 was involved in TNFalphapromoted osteogenic differentiation of human DPSCs through Wnt/betacatenin signal. In Vitro Cell Dev Biol Anim,2016,52:10011011.
[38]Iyer S,Han L,Bartell SM,et al. Sirtuin1(Sirt1)promotes cortical bone formation by preventingβcatenin sequestration by FoxO transcription factors in osteoblast progenitors. J Biol Chem,2014,289:2406924078.
[39]CohenKfir E,Artsi H,Levin A,et al. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin,a bone formation inhibitor. Endocrinology,2011,152:45144524.
[40]Fei Y,Shimizu E,McBurney MW,et al. Sirtuin 1 is a negative regulator of parathyroid hormone stimulation of matrix metalloproteinase 13 expression in osteoblastic cells:role of sirtuin 1 in the action of PTH on osteoblasts. J Biol Chem,2015,290:83738382.
[41]Xu Y,Wang S,Tang C,et al. Upregulation of long noncoding RNA HIF 1alphaantisense 1 induced by transforming growth factorbetamediated targeting of sirtuin 1 promotes osteoblastic differentiation of human bone marrow stromal cells. Mol Med Rep,2015,12:72337238.
[42]Kim YJ,Hwang SH,Lee SY,et al. MiR4865p induces replicative senescence of human adipose tissuederived mesenchymal stem cells and its expression is controlled by high glucose. Stem Cells Dev,2012,21:17491760.
[43]Gong K,Qu B,Liao D,et al. MiR132 regulates osteogenic differentiation via downregulating Sirtuin1 in a peroxisome proliferatoractivated receptor beta/deltadependent manner. Biochem Biophys Res Commun,2016,478:260267.
[44]Gong K,Qu B,Wang C,et al. Peroxisome proliferatoractivated receptor facilitates osteogenic differentiation in MC3T3E1cells via the sirtuin 1dependent signaling pathway. Mol Cells,2017,40:393400.
[2] Grabowska W,Sikora E,BielakZmijewska A. Sirtuins,a promising target in slowing down the ageing process. Biogerontology,2017,18:447476.
[3] Morris BJ. Seven sirtuins for seven deadly diseases of aging.Free Radic Biol Med,2013,56:133171.
[4] Sebastian C,Satterstrom FK,Haigis MC,et al. From sirtuin biology to human diseases:an update. J Biol Chem,2012,287:4244442452.
[5]吉鸿飞,秦贵军,张伟伟,等.叉头状转录因子O1对高糖培养大鼠肾小球系膜细胞氧化应激的影响.中华糖尿病杂志,2012,4:681685.
[6] Pulla VK,Battu MB,Alvala M et al. Can targeting SIRT1 to treat type 2 diabetes be a good strategy?a review. Expert Opin Ther Targets,2012,16:819832.
[7] Feng J,Liu S,Ma S,et al. Protective effects of resveratrol on postmenopausal osteoporosis:regulation of SIRT1NFkappaB signaling pathway. Acta Biochim Biophys Sin(Shanghai),2014,46:10241033.
[8] Xu C,Cai Y,Fan P,et al. Calorie restriction prevents metabolic aging caused by abnormal SIRT1 function in adipose tissues.Diabetes,2015,64:15761590.
[9] Braidy N,Guillemin GJ,Mansour H,et al. Age related changes in NAD+metabolism oxidative stress and sirt1 activity in wistar rats. PLoS One,2011,6:e19194.
[10]He X,Andersson G,Lindgren U,et al. Resveratrol prevents RANKLinduced osteoclast differentiation of murine osteoclast progenitor RAW 264. 7 cells through inhibition of ROS production. Biochem Biophys Res Commun,2010,401:356362.
[11]Zheng W,Feng Z,You S,et al. Fisetin inhibits IL1betainduced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. Int Immunopharmacol,2017,45:135147.
[12]Zhou Y,Song T,Peng J,et al. SIRT1 suppresses adipogenesis by activating Wnt/betacatenin signaling in vivo and in vitro. Oncotarget,2016,7:7770777720.
[13]Wang H,Kouri G,Wollheim CB. ER stress and SREBP1 activation are implicated in betacell glucolipotoxicity. J Cell Sci,2005,118:39053915.
[14]Kitamura YI,Kitamura T,Kruse JP,et al. FoxO1 protects against pancreatic beta cell failure through neurod and mafa induction. Cell Metab,2005,2:153163.
[15]Prud'homme GJ,Glinka Y,Udovyk O,et al. GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity. Biochem Biophys Res Commun,2014,452:649654.
[16]Chen YR,Lai YL,Lin SD,et al. SIRT1 interacts with metabolic transcriptional factors in the pancreas of insulinresistant and calorierestricted rats. Mol Biol Rep,2013,40:33733380.
[17]Bordone L,Motta MC,Picard F,et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreaticβcells. PLoS Biol,2006,4:e31.
[18]Jia L,Li W,Li J,et al. Lycium barbarum polysaccharide attenuates highfat dietinduced hepatic steatosis by upregulating SIRT1 expression and deacetylase activity. Sci Rep,2016,6:36209.
[19]Xu L,Kanasaki M,He J,et al. Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagyassociated molecules. Biochim Biophys Acta,2013,1832:16051612.
[20]Valdecantos MP,PerezMatute P,GonzalezMuniesa P,et al.Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. Obesity,2012,20:19741983.
[21]Liu J,Han W,Chen L,et al. Mechanism of osteogenic and adipogenic differentiation of tendon stem cells induced by sirtuin 1.Mol Med Rep,2016,14:16431648.
[22]Zhou X,Wang F,Yang H,et al. Seleniumenriched exopolysaccharides produced by Enterobacter cloacae Z0206 alleviate adipose inflammation in diabetic KKAy mice through the AMPK/SirT1 pathway. Mol Med Rep,2014,9:683688.
[23]Wende AR,Huss JM,Schaeffer PJ,et al. PGC1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha:a mechanism for transcriptional control of muscle glucose metabolism. Mol Cell Biol,2005,25:1068410694.
[24]Wu Z,Puigserver P,Andersson U,et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC1. Cell,1999,98:115124.
[25]Frojdo S,Durand C,Molin L,et al. Phosphoinositide 3kinase as a novel functional target for the regulation of the insulin signaling pathway by SIRT1. Mol Cell Endocrinol,2011,335:166176.
[26]Crandall JP,Oram V,Trandafirescu G,et al. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci,2012,67:13071312.
[27]JimenezGomez Y,Mattison JA,Pearson KJ,et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on highfat,highsugar diet. Cell Metab,2013,18:533545.
[28]Cao Y,Jiang X,Ma H,et al. SIRT1 and insulin resistance. J Diabetes Complications,2016,30:178183.
[29]GodfrinValnet M,Khan KA,Guillot X,et al. Sirtuin 1 activity in peripheral blood mononuclear cells of patients with osteoporosis. Med Sci Monit Basic Res,2014,20:142145.
[30]Hong W,Xu XY,Qiu ZH,et al. Sirt1 is involved in decreased bone formation in aged apolipoprotein Edeficient mice. Acta Pharmacol Sin,2015,36:14871496.
[31]Gurt I,Artsi H,CohenKfir E,et al. The sirt1 activators SRT2183 and SRT3025 inhibit ranklinduced osteoclastogenesis in bone marrowderived macrophages and downregulate Sirt3 in Sirt1 null cells. PloS one,2015,10:e0134391.
[32]Tseng PC,Hou SM,Chen RJ,et al. Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis. J Bone Miner Res,2011,26:25522563.
[33]Kim HN,Han L,Iyer S,et al. Sirtuin1 suppresses osteoclastogenesis by deacetylating FoxOs. Mol Endocrinol,2015,29:14981509.
[34]Li Y,Shen G,Yu C,et al. Angiotensin II induces mitochondrial oxidative stress and mtDNA damage in osteoblasts by inhibiting SIRT1–FoxO3a–MnSOD pathway. Biochem Biophys Res Commun,2014,455:113118.
[35]Backesjo CM,Li Y,Lindgren U,et al. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. Cells Tissues Organs,2009,189:9397.
[36]Kobayashi Y,Uehara S,Udagawa N,et al. Regulation of bone metabolism by Wnt signals. J Biochem,2016,159:387392.
[37]Feng G,Zheng K,Song D,et al. SIRT1 was involved in TNFalphapromoted osteogenic differentiation of human DPSCs through Wnt/betacatenin signal. In Vitro Cell Dev Biol Anim,2016,52:10011011.
[38]Iyer S,Han L,Bartell SM,et al. Sirtuin1(Sirt1)promotes cortical bone formation by preventingβcatenin sequestration by FoxO transcription factors in osteoblast progenitors. J Biol Chem,2014,289:2406924078.
[39]CohenKfir E,Artsi H,Levin A,et al. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin,a bone formation inhibitor. Endocrinology,2011,152:45144524.
[40]Fei Y,Shimizu E,McBurney MW,et al. Sirtuin 1 is a negative regulator of parathyroid hormone stimulation of matrix metalloproteinase 13 expression in osteoblastic cells:role of sirtuin 1 in the action of PTH on osteoblasts. J Biol Chem,2015,290:83738382.
[41]Xu Y,Wang S,Tang C,et al. Upregulation of long noncoding RNA HIF 1alphaantisense 1 induced by transforming growth factorbetamediated targeting of sirtuin 1 promotes osteoblastic differentiation of human bone marrow stromal cells. Mol Med Rep,2015,12:72337238.
[42]Kim YJ,Hwang SH,Lee SY,et al. MiR4865p induces replicative senescence of human adipose tissuederived mesenchymal stem cells and its expression is controlled by high glucose. Stem Cells Dev,2012,21:17491760.
[43]Gong K,Qu B,Liao D,et al. MiR132 regulates osteogenic differentiation via downregulating Sirtuin1 in a peroxisome proliferatoractivated receptor beta/deltadependent manner. Biochem Biophys Res Commun,2016,478:260267.
[44]Gong K,Qu B,Wang C,et al. Peroxisome proliferatoractivated receptor facilitates osteogenic differentiation in MC3T3E1cells via the sirtuin 1dependent signaling pathway. Mol Cells,2017,40:393400.