Effect of celecoxib on the expression of related factors and biomechanics of Achilles tendon in traumatic heterotopic ossification
Objective To investigate the effect of celecoxib on the expression of related factors and biomechanics of Achilles tendon in traumatic heterotopic ossification(HO).Methods A total of 60 rabbits were divided into normal group,model group,celecoxib low-dose group,celecoxib high-dose group,celecoxib 3-week treatment group,and celecoxib 6-week treatment group,with 10 rabbits in each group.The traumatic HO model was established in all rabbits except those in the normal group.After successful modeling,celecoxib low-dose and high-dose groups were given 20 and 60 mg/(kg·d)celecoxib by gavage,for continuous 10 days,respectively.Celecoxib 3-week and 6-week treatment groups were given 10 mg/(kg·d)celecoxib by gavage for continuous 3,and 6 weeks,respectively.Normal group and model group were both given 2 mL 0.9％sodium chloride solution by gavage for continuous 10 days.Serum CRP levels were detected by ELISA kit.The skin temperature of limbs was recorded by skin thermometer,and the swelling degree was evaluated by limb swelling score.X-ray film was taken to observe the new bone formation.The biomechanical parameters of the right Achilles tendon of rabbits were measured by three-point bending test.Bone morphogenetic protein(BMP)-2 and BMP-4 in Achilles tendon were detected by qRT-PCR.Cyclooxygenase-2(COX-2)of Achilles tendon was detected by immunohistochemistry.The expression levels of transforming growth factor-β(TGF-β)1 and Smad1 in Achilles tendon tissues were detected by Western blot method.Results Compared with normal group,serum CRP level,average skin temperature,swelling degree and new bone formation score,mRNA expression levels of BMP-2 and BMP-4 in Achilles tendon tissue,gray value of COX-2,and protein expression levels of TGF-β1 and Smad1 in model group were increased(all P＜0.05).The maximum load,flexural strength,elastic load,and rigidity coefficient of the right Achilles tendon were decreased(all P＜0.05).Compared with model group,the above indicators were all decreased in celeoxib low-and high-dose groups and celeoxib 3-and 6-week treatment groups(all P＜0.05),while the maximum load,flexural strength,elastic load and rigidity coefficient of the right Achilles tendon were all increased(all P＜0.05).Compared with celeoxib low-dose group,serum CRP level,average skin temperature,swelling degree and new bone formation score,mRNA expression levels of BMP-2 and BMP-4 in Achilles tendon tissue,gray value of COX-2,and protein expression levels of TGF-β1 and Smad1 in celeoxib high-dose group were decreased(all P＜0.05).There were no statistical significances in the pairwise comparison of the above indexes between celecoxib 3-,6-week treatment groups and celecoxib low-dose group(all P＞0.05).Conclusion Celeoxib can improve the biomechanics and reduce the inflammatory response of traumatic HO rabbits at different doses and time.The mechanism of action may be related to down-regulation of the expression levels of COX-2,BMP-2 and BMP-4 in Achilles tendon tissue and inhibition of the activity of TGF-β/Smads signaling pathway.
CelecoxibTraumatic heterotopic ossificationCyclooxygenase-2Bone morphogenetic protein
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维普
