Effect of dehydroepiandrosterone on the balance of ADAMTS/tissue inhibitor of metalloproteinases-3 system in rabbit osteoarthritis models / 中华风湿病学杂志

ABSTRACT

Objective To study the effect of intra-articular injection of dehydroepiandrosterone (DHEA) on the balance of ADAMTS/TIMP-3 system in a rabbit osteoarthritis models.Methods Sixty rabbits were underwent bilateral anterior cruciate ligament transection (ACLT).Rabbits were randomizedn to the following treatmentone knee of each rabbit was treated with 100 μmol/L DHEA dissolved in dimethylsulphoxide (the experimental group) and the other knee was treated under the same schedule using dimethylsulphoxide (the control group) 4 weeks after transection,once a week for eight weeks.Twelve weeks after ACLT,all rabbits were killed after X-ray assessment and the knee joints were evaluated by gross morphology and histology.The concentration of hydroxyproline and glycosaminoglycan in the cartilage were analyzed.The mRNA expression of ADAMTS-4,ADAMTS-5,tissue inhibitor of metalloproteinases-3 (TIMP-3),transforming growth factor (TGF)-β1.Aggrecan and Collagen Ⅱ in the cartilage were analyzed using reverse transcription polymerase chain reaction (RT-PCR).The protein expression of aggrecan ARGxx and Collagen Ⅱ in the cartilage were analyzed by Western blot.Results By Mann-Whitney test,Gross morphologic scores on femoral condyle and tibial plateau in the control group were significantly higher than the experi-mental group (Z=-3.517,P＜0.01 ; Z=-2.518,P＜0.05).By unpaired Student's t test,histological evaluation showed that the grade of cartilage damage in the experimental group [(5.3±1.2) μg/ml] were less severe than that in the control group (10.1 ± 1.3,P＜0.01).The concentration of hydroxyproline [(5.7±0.3,23.6± 1.7) μg/ml] and glycosaminoglycan (30±4) in the experimental group increased significantly when compared with the control group [(4.6±0.5),(18.5±1.4),(24±4) μg/ml,P＜0.01].The mRNA expression of ADAMTS-4 (0.15±0.03)and ADAMTS-5 (0.10±0.04) in the experimental group decreased significantly compared with the control group (0.29±0.08,0.15±0.05; all P＜0.05).The mRNA expression of TIMP-3 (0.85±0.10),TGF-β1(1.2±0.4),Aggrecan (0.87±0.31) and Collagen Ⅱ (2.74±0.59) in the experimental group increased significantly when compared with the control group (0.70±0.13,0.8±0.4,0.49±0.16,2.2±0.5; all P＜0.05).The protein expression of Aggrecan ARGxx (0.53±0.10) in the experimental group decreased significantly when compared with the control group (0.81±0.12,P＜0.01).The protein expression of Collagen Ⅱ (2.3±0.7) in the experimental group increased significantly when compared with the control group (1.7±0.5,P＜0.05).Conclusion DHEA protects against cartilage degradation and inhibits the progression of OA,TGF-β1,Aggrecan and Collagen Ⅱ in cartilage may be the mechanism of the protective effect of DHEA on OA.