Effect Of Indomethacin On Expression Of Sclerostin And COX-2 In The Formation Of Heterotopic Ossification After Trauma In Rats

Objective: To investigate the effects of indomethacin on the expression of sclerostin(SO)and COX-2 in the traumatic heterotopic ossification(HO)in rats and its influence on the formation of HO,to provide basis for clinical diagnosis,prevention and treatment of HO.Methods: 1.30 male SPF SD(Sprague Dawley)rats were selected and underwent X-ray examination on left legs and among them,5 rats were randomly selected to take blood serum SO level was measured by ELISA and were put back into the cage.After being feed adaptively for one week,the rats were randomly divided into experimental group of ten,model group of ten,and control group of ten,respectively.In aseptic conditions,achilles tenotomy in the left hind leg was conducted among the rats in experimental group and the model group to induce the HO model while the control group just underwent skin incision instead of the achilles tendon cutting.The experimental group rats took 10 mg/(kg·d)indomethacin concentrated solution by gavage for 4 weeks,while the model group and the control group rats were given an equal volume of saline.2.In the fifth and tenth week after modeling,each group took X-ray to evaluate the changes of density in their left achilles tendons;The content of serum SO 5 was measured by ELISA in five rats from each group;For each group,five rats were sacrificed for gross morphological observation of give their left achilles tendons,HE staining and immunohistochemistry to detect the expression of COX-2,respectively.Data were expressed by mean±standard deviation,and analyzed by SPSS16.0 statistical software with test level alpha =0.05.Results: 1.The comparison of X-rays in the fifth week showed that,the model group(n = 7)and the experimental group(n = 2)showed ossification,which was not observed in the control group.The comparison of COX-2 showed the positive expression of COX-2 in the model group and had statistical significance compared with the control group(P<0.05);COX-2 in experimental group was weakly positive,and was statistically significant compared with the model group(P<0.05);COX-2 in control group was negative or weakly positive,lacking statistical significance.the comparison of SO showed that the level of SO in model group was lower than before modeling,and was lower than that in control group and the experimental group(P<0.05);the experimental group showed increased SO concentration,which offered statistical significance compared with the control group(P<0.05);the change of serum SO concentration in control group had no statistical significance(P>0.05).2.The comparison of X-rays in the tenth week showed that,the model group(n = 5)and the experimental group(n = 2)showed ossification,which was not observed in the control group.The comparison of COX-2 showed the strongly positive expression of COX-2 in the model group and had statistical significance compared with the control group(P<0.05);COX-2 in experimental group was weakly positive,and was statistically significant compared with the model group(P<0.05);COX-2 in control group was negative or weakly positive.The comparison of SO showed that The level of SO in model group.was lower than before modeling,and was lower than that in control group and the experimental group(P<0.05);the experimental group showed increased SO concentration,which was statistically significant compared with the control group(P<0.05);the serum SO concentration in control group didn't change obviously(P>0.05).Conclusions: 1.The down-regulation of serum SO may lead to the formation of HO.2.The local increase of osteogenic factor COX-2 in HO may promote the formation of HO.3.Indomethacin may help inhibit HO through upregulation of SO and downregulation of COX-2 expression.