| Objective:L-Carnitine(LC)is an essential nutrient with a major role in cellular energy production.The present study was undertaken to determine whether LC regulates serum deprivation or the dexamethasone(Dex)-induced apoptosis of osteoblastic MC3T3-E1 cells, and to examine the mechanisms by which LC acts on cell apoptosis. Pharmacological GC-induced bone loss,another aim of our study was to characterize the effects of LC on BMD and bone microarchitecture of GC-induced bone loss rat model.Methods:(1)murine MC3T3-E1 osteoblastic cells were treated with or without 10-5 to 10-2 M LC.Cell apoptosis was measured by Cell Death Detection ELISA kit.Release of cytochrome c from mitochondria into cytosol and Bcl-2,Bax protein levels were determined by Western blot analysis.The enzyme substrate was used to assess the activation of caspase-3 and caspase-9.(2)The isolated BMD and BMC of lumbar vertebrae(L3-L5) and the left femur were measured by DXA.The microarchitecture of the left tibia was detected byμCT.Results:(1) 10-4 to 10-2M LC protected MC3T3-E1 cells against serum deprivation-induced apoptosis;10-4 to 10-2M LC inhibited cytochrome c release and decreased activated caspase-3 and caspas-9;LC inhibited Dex-induced apoptosis of MC3T3-E1 cells.(2) There was an insignificant decrease in body weight in GCT group,and compared with the GCT group,there was an insignificant increase in LC group.There were decreases in BMD and BMC of the left femur and the lumbar vertebrae in GCT group.Besides,compared with the GCT group, there were increases in BMC of the left femur and BMD of the lumbar vertebar in LC group(P＜0.05).There were decreases in Tb.N,BVF,vBMD,Conn.D,and increases in Tb.Th and Tb.Sp in GCT group(P＜0.01).Besides,compared with the GCT group,there were increases in Tb.N,BVF and Conn.D(P＜0.01),and decreases in Tb.Th(P＜0.05) and Tb.Sp(P＜0.01) in LC group.Conclusions:(1) LC protects serum-deprived MC3T3-E1 cells from apoptosis by inhibiting of cytochrome c release and caspase-3 and caspase-9 activation;(2) LC inhibits Dex-induced apoptosis of MC3T3-E1 cells;(3) LC increases BMD and BMC of GC-induced bone loss rat model,and improves their bone microarchitectures. |
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