目的 探讨鸢尾素对兔骨髓间充质干细胞(bone-marrow mesenchymal stem cells,BMSCs)成脂分化的影响及其信号机制。方法 分离、培养兔BMSCs,检测鸢尾素对BMSCs增殖的影响。BMSCs成脂诱导后,实时荧光定量PCR(polymerase chain reaction,PCR)检测成脂相关基因PPARγ和C/EBPα的转录表达,油红O染色检测细胞内脂质形成情况,Western blot检测Wnt10a信号蛋白的表达。结果 鸢尾素不影响BMSCs的增殖活性;显著下调PPARγ[成脂诱导第7天,(0.20±0.06)vs(1.00±0.10);成脂诱导第14天,(0.61±0.06)vs(1.00±0.15)]和C/EBPα[成脂诱导第7天,(0.40±0.06)vs(1.00±0.12);成脂诱导第14天,(0.70±0.09)vs(1.00±0.18)]的表达,明显抑制BMSCs成脂分化[(0.45±0.05)vs(0.95±0.10);P<0.05];同时,鸢尾素明显促进Wnt10a表达[(5.01±0.78)vs(1.00±0.25);P<0.05]。结论 鸢尾素可抑制BMSCs脂向分化,其作用与激活Wnt信号通路有关。
Abstract
Objective To investigate the effects of irisin on adipocyte differentiation of BMSCs from rabbits and related mechanisms. Methods BMSCs of rabbits were extracted and proliferation capacity was detected. After BMSCs were cultured in adipogenesis medium supplemented with or without irisin, qPCR was used to evaluate the expression levels of PPARγ and C/EBPα, while oil red O staining was used to investigate fat accumulation. The signaling protein level of Wnt10a was detected by Western blot. Results Proliferation capacity of BMSCs was hardly affected by irisin. Irisin could significantly downregulate mRNA expressions of PPARγ [(0.20±0.06) vs (1.00±0.10) 7 days after adipogenesis induction and(0.61±0.06) vs (1.00±0.15) 14 days after adipogenesis induction]and C/EBPα [(0.40±0.06) vs (1.00±0.12) 7 days after adipogenesis induction and (0.70±0.09) vs (1.00±0.18) 14 days after adipogenesis induction], while attenuating fat accumulation [(0.45±0.05) vs (0.95±0.10),P<0.05]. Moreover, Wnt10a protein levels were increased by irisin intervention[(5.01±0.78) vs (1.00±0.25),P<0.05]. Conclusions Irisin can inhibit adipocyte differentiation of BMSCs from rabbits, and this effect is related to activation of Wnt signaling pathway.
关键词
鸢尾素 /
成脂 /
骨髓间充质干细胞
Key words
irisin /
adipogenesis /
bone-marrow mesenchymal stem cells
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Meng J, Ma X, Wang N,et al.Activation of GLP-1 receptor promotes bone marrow stromal cell osteogenic differentiation through β-catenin[J].Stem Cell Rep, 2016, 6(4): 579-591.
[2] D'Alimonte I, Lannutti A, Pipino C,et al.Wnt signaling behaves as a “master regulator” in the osteogenic and adipogenic commitment of human amniotic fluid mesenchymal stem cells[J].Stem Cell Rev Rep, 2013, 9(5): 642-654.
[3] Yang Y, Tan Y, Wong R,et al.The role of vascular endothelial growth factor in ossification[J].Int J Oral Sci, 2012, 4(2): 64-68.
[4] Liu G, Vijayakumar S, Grumolato L,et al.Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells[J]. J cell biol, 2009, 185(1): 67-75.
[5] Moseti D, Regassa A, Kim W.Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules[J].Int J Mol Sci, 2016, 17(1): 124.
[6] Rosen E D, MacDougald O A.Adipocyte differentiation from the inside out[J]. Molecul cell biol, 2006, 7(12): 885-896.
[7] Boström P, Wu J, Jedrychowski MP,et al.A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J].Nature, 2012, 481(7382): 463-468.
[8] 李金儒, 位 朵, 甄国朋,等.Irisin对高糖环境中BMSCs骨向分化的影响及机制研究[J].华南国防医学杂志, 2019, 33(07): 445-449.
[9] 郭 滨, 甄国朋, 杨海青,等.Irisin对老龄性骨质疏松小鼠骨代谢的影响及机制研究[J].解放军医药杂志, 2019, 31(12): 23-28.
[10] Qiao X, Nie Y, Ma Y,et al.Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways[J].Sci Rep-UK, 2016, 6: 18732.
[11] Ma E B, Sahar N E, Jeong M,et al.Irisin Exerts Inhibitory Effect on Adipogenesis Through Regulation of Wnt Signaling[J].Front Physiol, 2019, 10: 1085.
[12] 朱 彪, 张欣然, 赵 刚,等.以ADSCs替代BMMSCs构建组织工程骨修复种植区骨缺损的实验研究[J].牙体牙髓牙周病学杂志, 2015, 25(11): 651-658.
[13] 刘 婷, 张承英, 苏静克,等.GDF 11改善老龄鼠内皮依赖性血管舒张功能的实验研究[J].武警医学, 2018, 29(7): 702-705.
[14] Huh J Y.The role of exercise-induced myokines in regulating metabolism[J].Arch Pharm Res, 2018, 41(1): 14-29.
[15] Pedersen B K, Febbraio M A.Muscles, exercise and obesity: skeletal muscle as a secretory organ[J]. Endocrinol, 2012, 8(8): 457-465.
[16] Łukaszuk B, Kurek K, Mikłosz A,et al.The Role of PGC-1α in the Development of Insulin Resistance in Skeletal Muscle - Revisited[J].Cell Physiol Biochemist, 2015, 37(6): 2288-2296.
[17] Panati K, Suneetha Y, Narala V R.Irisin/FNDC5--An updated review[J].Eur Rev Med Pharmaco, 2016, 20(4): 689-697.
[18] Huh J Y, Dincer F, Mesfum E,et al.Irisin stimulates muscle growth-related genes and regulates adipocyte differentiation and metabolism in humans[J].J Obes(2005), 2014, 38(12): 1538-1544.
[19] Zhang Y, Xie C, Wang H,et al.Irisin exerts dual effects on browning and adipogenesis of human white adipocytes[J].J Physiol, 2016, 311(2): E530-E541.
[20] Cawthorn W P, Bree A J, Yao Y,et al.Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanism[J].Bone, 2012, 50(2): 477-489.
[21] Zhang J, Valverde P, Zhu X,et al.Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism[J].Bone Res, 2017, 5: 16056.
[22] Geng Z, Fan W, Zhou B,et al.FNDC5 attenuates obesity-induced cardiac hypertrophy by inactivating JAK2/STAT3-associated inflammation and oxidative stress[J].J Transl Med, 2019, 17(1): 107.
PDF(750 KB)
