地塞米松对护骨素基因敲除小鼠骨微结构的影响

The effect of dexamethasone on bone micro-architecture in OPG^(-/-) mice

目的探讨小剂量地塞米松对生长期小鼠骨密度及骨微结构的影响及其与OPG途径的关系。方法 20只4周龄OPG^(-/-)雌性小鼠及20只野生型小鼠随机分四组(n=10):野生型安慰剂组(WT+saline),野生型地塞米松干预组(WT+DEX,地塞米松1mg/kg体重,肌肉注射,每周3次),OPG^(-/-)敲除小鼠安慰剂组(OPG^(-/-)+saline),OPG^(-/-)敲除小鼠DEX干预组(OPG^(-/-)+DEX,地塞米松1 mg/kg体重,肌肉注射,每周3次)。6周后处死小鼠,一侧胫骨行显微CT扫描分析。结果OPG^(-/-)组的组织骨密度、骨小梁体积分数、骨小梁数量、骨小梁厚度均较其他三组降低(P<0.05)。OPG^(-/-)+DEX组的组织骨密度、骨小梁体积分数、骨小梁数量、骨小梁厚度均较WT及WT+DEX组降低(P<0.05)。OPG^(-/-)组的骨小梁模型因子及骨小梁分离度均较其他三组增加(P<0.05);OPG^(-/-)+DEX组的骨小梁模型因子及骨小梁分离度均较WT及WT+DEX组增加(P<0.05)。WT及WT+DEX组之间骨小梁微结构参数均无统计学差异。结论在生长期小鼠OPG基因功能缺失时,地塞米松有部分拮抗骨量丢失的作用,表明除了OPG/RANKL途径,地塞米松对骨代谢的影响是多途径的。

Obje ctive To observe the effect of low-dose dexamethasone on bone mineral density and micro-architecture in grow ing mice w ithout OPG gene. Me thods Tw enty 4-w eek-old female OPG^-/-mice and tw enty 4-w eek-old w ild type mice w ere randomly assigned to 4 groups（ n = 10） ： w ild type and placebo group（ WT ＋ saline）,w ild type and dexamethasone group（ WT ＋DXM,1mg / kg,intramuscular injection,3 times / w）, OPG^-/-and placebo group（ OPG^-/-＋ saline）, and OPG^-/-and dexamethasone group（ OPG^-/-＋ DEX,1mg / kg,intramuscular injection,3 times / w）. The mice w ere sacrificed after 6 w eeks.One side of the tibia of each mouse w as selected for micro-CT analysis. Re sults Tb. N,BS / BV,Tb. Th,and t BM D significantly decreased in OPG^-/-mice than those in the other three groups（ P〈0. 05）. Tb. N,BS / BV,Tb. Th,and t BM D significantly decreased in OPG^-/-＋ DEX mice than those in WT and WT ＋ DEX mice（ P〈0. 05）. Tb. Pf and Tb. Sp significantly increased in OPG^-/-mice than those in the other three groups（ P〈0. 05）. Tb. Pf and Tb. Sp significantly increased in OPG^-/-＋ DEX mice than those in WT and WT ＋ DXM mice（ P〈0. 05）. BM D and bone micro-architecture parameters w ere not significantly different betw een WT and WT ＋ DXM mice. Conclusion Dexamethasone partly extenuates the bone loss in grow ing mice w ithout OPG gene function. It indicates that in addition to OPG / RANKL pathw ay,dexamethasone affects bone metabolism through multiple pathw ays.