Effects of paricalcitol on bone metabolism and TGF-β/BMP-7/Smad signaling pathway in rats with renal osteodystrophy
Objective:To investigate the effects of paricalcitol on bone metabolism and transforming growth factor-β(TGF-β)/bone morphogenetic protein-7(BMP-7)/Smad signaling pathway in rats with renal osteodystrophy(ROD).Methods:Total 90 rat were randomly divided into 6 groups:control group,model group,paricalcitol low-dose(0.2 µg/kg)group,paricalcitol medium-dose group(0.4 µg/kg)group,paricalcitol high-dose(0.8 µg/kg)group,calcitriol(10 µg/kg)group,with 15 rats in each group.Rats in control group were fed with ordinary feed,and rats in other groups were fed with feed containing adenine to induce the establishment of ROD model.After grouping and drug treatment,the blood urea nitrogen(BUN)and blood creatinine(Scr)levels,blood calcium and blood phosphorus levels,femoral bone mineral density(BMD),maximum load,elasticity modulus and yield load,serum inflammatory fac-tors IL-6 and IL-17 levels of each group were measured;and the expression of TGF-β/BMP-7/Smad pathway protein in bone tissue was detected with Western blot.Another 45 rats were randomly divided into 3 groups:paricalcitol(0.8 µg/kg)group,TGF-β inhibition(LY2157299,150 mg/kg)group,paricalcitol(0.8 µg/kg)+TGF-β inhibition(LY2157299,150 mg/kg)group,with 15 rats in each group.ROD model was established with the same method.After drug treatment,the renal function indexes and femoral biomechanical indexes were measured.Results:Compared with control group,the blood calcium level,BMD,elastic modulus,maximum load,yield load,bone tissue TGF-β/BMP-7/Smad pathway proteins TGF-β and BMP-7 expressions,p-Smad3/Smad3 were significantly re-duced in the model group(P<0.05),the BUN and Scr levels,blood phosphorus level,and serum IL-6 and IL-17 levels were signifi-cantly increased(P<0.05).Compared with the model group,the blood calcium level,BMD,elastic modulus,maximum load,yield load,bone tissue TGF-β/BMP-7/Smad pathway protein TGF-β and BMP-7 expression,p-Smad3/Smad3 were significantly increased in the paricalcitol low,medium and high dose groups and calcitriol group(P<0.05),the BUN and Scr levels,blood phosphorus level,and serum IL-6 and IL-17 levels were significantly reduced,and paricalcitol groups showed a dose-dependent relationship(P<0.05),there was no significant difference in the indexes of rats in high-dose paricalcitol group and calcitriol group(P>0.05).Compared with paricalcitol+TGF-β inhibition group,the renal function indexes BUN,SCR and blood phosphorus level in paricalcitol group were de-creased(P<0.05),while the blood calcium level,BMD,elastic modulus,maximum load and yield load were increased(P<0.05).In TGF-β inhibition group,the renal function indexes BUN,SCR and blood phosphorus levels were increased(P<0.05),while the blood calcium level,BMD,elastic modulus,maximum load and yield load were decreased(P<0.05).Conclusion:Paricalcitol can activate the TGF-β/BMP-7/Smad signaling pathway,inhibit inflammation,improve renal function and abnormal bone metabolism in ROD rats,reduce blood phosphorus level,increase blood calcium level and bone density,repair bone biomechanics,and improve the symptoms of osteodystrophy.
ParicalcitolRenal osteodystrophyBone metabolismTransforming growth factor-β/bone morphogenetic protein-7/Smad signal
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