Significance of JAK-STAT signaling pathway in steroid-induced osteonecrosis of femoral head
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[目的]探讨Janus激酶-信号转导和转录激活因子信号通路(Janus kinase-signal transducer and activator of transcrip-tion signaling pathway,JAK-STAT signaling pathway)与激素性股骨头坏死发生机制之间的关联.[方法]体内试验,36只Sprague-Dawley(SD)大鼠按随机分为三组,每组12只,分别为空白对照组、模型组和干预组,给予相应药物处理,行股骨头HE染色和TUNEL染色.体外试验,自幼鼠颅骨分离成骨细胞,分为同体内试验相同的三组,给予相应体外处理,检测ALP和JAK-STAT通路蛋白p-JAK2、p-STAT3蛋白表达水平.[结果]体内试验,HE染色骨空隐窝率由高至低依次为:模型组＞干预组＞对照组,差异有统计学意义[(38.9±1.3)％vs(18.9±0.9)％vs(3.2±0.6)％,P＜0.001];TUNEL染色细胞凋亡率依次为:模型组＞干预组＞对照组,差异有统计学意义[(42.2±2.7)％vs(16.1±1.3)％vs(6.2±1.1)％,P＜0.001].体外试验,TUNEL染色细胞凋亡率由高至低依次为:模型组＞干预组＞对照组,差异有统计学意义[(42.3±3.5)％vs(18.2±1.6)％vs(10.2±1.3)％,P＜0.001];ALP由低至高依次为:模型组＜干预组＜对照组,差异有统计学意义[(53.6±7.7)IU vs(79.2±6.5)IU vs(92.4±4.4)IU,P=0.037].此外,模型组JAK-STAT 相关标志蛋白表达均显著高于对照组和干预组,p-JAK2[(1.6±0.2),(1.0±0.1),(1.3±0.3),P＜0.05]、p-STAT[(1.4±0.2),(1.0±0.1),(1.2±0.3),P＜0.05],差异具有统计学意义.[结论]JAK-STAT信号通路特异性抑制剂AG490可抑制激素引发细胞凋亡,其机理可能与抑制p-JAK2和p-STAT蛋白表达有关.
[Objective]To investigate the relationship of the Janus kinase-signal transducer and activator of transcription(JAK-STAT)signaling pathway with the pathogenesis of steroid-induced osteonecrosis of femoral head.[Methods]In vivo experiment,36 Sprague-Daw-ley(SD)rats were randomly divided into three groups with 12 animals in each group,including the blank control group,model group and in-tervention group,which were treated with corresponding drugs respectively.The femoral head was harvest for HE and TUNEL staining 28 days later.In vitro test,osteoblasts were separated from the skull of a young rat and divided into three groups as in vivo test.After correspond-ing treatments were given in vitro,the expression levels of ALP and JAK-STAT pathway related protein,such as JAK2 and p-STAT3,were assessed.[Results]In vivo test,the rates of empty bone crypts revealed by HE stain was ranked up-down as follows:the model group＞the intervention group＞the control group,with a statistically significant difference[(38.9±1.3)％ vs(18.9±0.9)％ vs(3.2±0.6)％ ,P＜0.001],like-ly,the apoptosis rates showed by TUNEL stain was of the model group＞the intervention group＞the control group,with a statistically signifi-cant different[(42.2±2.7)％ vs(16.1±1.3)％ vs(6.2±1.1)％ ,P＜0.001].In vitro test,apoptosis rate by TUNEL staining was ranked as:the mod-el group＞the intervention group＞the control group and the difference was statistically significant[(42.3±3.5)％ vs(18.2±1.6)％ vs(10.2±1.3)％ ,P＜0.001],whereas the ALP activity was ranked from low to high as:the model group＜the intervention group＜the control group with a statistically significant difference[(53.6±7.7)IU vs(79.2±6.5)IU vs(92.4±4.4)IU,P=0.037].In addition,JAK-STAT-related marker pro-tein expression in model group was significantly higher than that in the control group and the intervention group,including p-JAK2[(1.6±0.2)vs(1.0±0.1)vs(1.3±0.3),P＜0.05]and p-STAT[(1.4±0.2)vs(1.0±0.1)vs(1.2±0.3),P＜0.05].[Conclusion]The JAK-STAT signaling pathway specific inhibitor AG490 does inhibit steroid-induced cell apoptosis,its mechanism may be related to the inhibition of p-JAK2 and p-STAT protein expression.
femoral head necrosispathogenesisJAK-STAT signaling pathway
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