地塞米松影响大鼠成骨细胞脂质分化相关基因表达的实验观察
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摘要
目的探讨地塞米松作用下成骨细胞脂质分化及成骨相关基因的表达变化特点。方法将SD大鼠颅骨成骨细胞作为研究对象,观察在应用不同浓度的地塞米松、甘珀酸分别作用于成骨细胞,其脂质与成骨分化标志基因、成骨标志基因的表达变化。结果应用地塞米松后成骨细胞内发生脂质积聚,成脂分化标志基因PPARγ、C/EBPα表达上调,成骨相关的runx2、Col.1、OPG相关基因无上调改变。应用甘珀酸后未见上述基因表达的逆转改变。结论成骨细胞在受到皮质激素作用后可产生脂质异常积聚,可能与其PPARγ、C/EBPα表达上调有关。
Objective To investigate the rat osteoblast lipid differentiation under dexamethasone action and osteogenesis related gene expression change characteristics.Methods The cranial osteoblasts,of SD rats were adopted as the study objects.The lipids and osteogenesis differentiation marker gene were observed after different concentrations of dexamethasone acting on osteoblasts and under the status of carbenoxolone use,as well as the expression change of osteoblast marker gene,and their relationship was analyzed.Results The lipid deposition occurred within osteoblasts after using dexamethasone.The expressions of adipogenic differentiation marker genes PPARγand C/EBPαwere up regulated,while the osteoblastic related genes(runx2,Col.1 and OPG)had no up regulation change.The reversing change of above genes expressions was not found after using carbenoxolone.Conclusion Abnormal lipid deposition in osteoblasts could be induced after dexamethasone acting on osteoblasts,which maybe related to the PPARγand C/EBPαexpression up regulation.The adipogenic differentiation gene expression is not affected by carbenoxolone in vitro.
Objective To investigate the rat osteoblast lipid differentiation under dexamethasone action and osteogenesis related gene expression change characteristics.Methods The cranial osteoblasts,of SD rats were adopted as the study objects.The lipids and osteogenesis differentiation marker gene were observed after different concentrations of dexamethasone acting on osteoblasts and under the status of carbenoxolone use,as well as the expression change of osteoblast marker gene,and their relationship was analyzed.Results The lipid deposition occurred within osteoblasts after using dexamethasone.The expressions of adipogenic differentiation marker genes PPARγand C/EBPαwere up regulated,while the osteoblastic related genes(runx2,Col.1 and OPG)had no up regulation change.The reversing change of above genes expressions was not found after using carbenoxolone.Conclusion Abnormal lipid deposition in osteoblasts could be induced after dexamethasone acting on osteoblasts,which maybe related to the PPARγand C/EBPαexpression up regulation.The adipogenic differentiation gene expression is not affected by carbenoxolone in vitro.
引文
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[14]CHOI C I.Astaxanthin as a Peroxisome proliferator-activated receptor(PPAR)modulator:Its therapeutic implications[J].Mar Drugs,2019,17(4):E242.
[2]LI Y H,GAO F Q,CHENG L M,etal.Different changes of microarchitectures of cortical and cancellous bones in sheep femoral head after long-term glucocorticoid interventions[J].Sci Rep,2018,8(1):9988.
[3]MURATA M,KUMAGAI K,MIYATA N,et al.Osteonecrosis in stroke-prone spontaneously hypertensive rats:effect of glucocorticoid[J].J Orthop Sci,2007,12(3):289-295.
[4]KAWAI K,TAMAKI A,HIROHATA K.Steroid-induced accumulation of lipid in the osteocytes of the rabbit femoral head.A histochemical and electron microscopic study[J].J Bone Joint Surg Am,1985,67(5):755-763.
[5]PU R,PENG H.11β-hydroxysteroid dehydrogenases as targets in the treatment of steroid-associated femoral head necrosis using antler extract[J].Exp Ther Med,2018,15(1):977-984.
[6]FRIED A,BENAYAHU D.Dexamethasone regulation of marrow stromal-derived osteoblastic cells[J].J Cell Biochem,1996,62(4):476-483.
[7]JONES J P,ENGLEMAN E P,NAJARIAN J S.Systemic fat embolism after renal homotransplantation and treatment with corticosteroids[J].N Engl J Med,1965,273(27):1453-1458.
[8]KAWAI K,MARUNO H,WATANABE Y,et al.Fat necrosis of osteocytes as a causative factor in idiopathic osteonecrosis in heritable hyperlipemic rabbits[J].Clin Orthop Relat Res,1980(153):273-282.
[9]HU C G,LIU Q,CHEN J C,et al.Cytological changes of femoral head necrosis induced by glucocorticoid[J].Chinese J Rehanilitation,2006,10(1):97-99.
[10]HONG D,CHEN H X,GE R S,et al.The biological roles of extracellular and intracytoplasmic glucocorticoids in skeletal cells[J].J Steroid Biochem Mol Biol,2008,111(3/5):164-170.
[11]ALAM I,OAKES D K,REILLY A M,et al.Overexpression of WNT16does not prevent cortical bone loss due to glucocorticoid treatment in mice[J].JBMR Plus,2018,3(4):e10084.
[12]JIN Q H,ZHANG F,YAN T G,et al.C/EBPalpha regulates SIRT1expression during adipogenesis[J].Cell Res,2010,20(4):470-479.
[13]AHMAD F,SOELAIMAN I N,RAMLI E S,et al.Histomorphometric changes in the perirenal adipocytes of adrenalectomized rats treated with dexamethasone[J].Clinics(Sao Paulo),2011,66(5):849-853.
[14]CHOI C I.Astaxanthin as a Peroxisome proliferator-activated receptor(PPAR)modulator:Its therapeutic implications[J].Mar Drugs,2019,17(4):E242.
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