Effect of dehydroepiandrosterone on experimental osteoarthritis in rabbits
Li Wu
Abstract
Li Wu
Abstract
Objective To observe the effect of intra-articular injection of dehydroepiandrosterone (DHEA)on the experimental osteoarthritis in rabbits and study the mechanism.Methods Forty rabbits un derwent unilateral anterior cruciate ligament transection(ACLT)and then divided into two groups randomly. 100μmol/L DHEA resolved in the dimethylsulphoxide were injected into the knees of experimental rabbits 4 weeks after transection,once a week for five weeks.Rabbits in the control group were treated under the same schedule using dimethylsulphoxide.All rabbits were killed 9 weeks after ACLT and the knee joints were evalu- ated by gross morphology and histology.The mRNA expression of metalloproteinases-3(MMP-3),tissue in- hibitor of metalloproteinases-1(TIMP-1)and interleukin-lbeta(IL-1β)in the cartilage and synovium was analyzed using reverse transcription polymerase chain reaction(RT-PCR).Results Gross morphologic in- spection and histological evaluation showed that the extent and grade of cartilage and synovium damage in the experimental group were less severe than the control group.The mRNA expression of MMP-3 in cartilage and synovium decreased significantly in the experimental group(both P<0.05).The mRNA expression of TIMP-1 in cartilage and synovium increased significantly in the experimental group compared with that in the control group(both P<0.05).No significant difference of IL-1βmRNA expression in cartilage was found between the experimental and the control groups(P>0.05).The mRNA expression of IL-1βin the synovium was signifi- cantly suppressed in the experimental group compared with that in the control group(P<0.01).Conclusion DHEA protects against cartilage degradation,alleviates synovium inflammation and inhibits the progression of osteoarthritis in the experimental model.Down-regulation of MMP-3 and up-regulation of TIMP-1 in cartilage and synovium and IL-1βin the synovium may be the mechanism of the protective effect of DHEA on os- teoarthritis.
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Objective To observe the effect of intra-articular injection of dehydroepiandrosterone (DHEA)on the experimental osteoarthritis in rabbits and study the mechanism.Methods Forty rabbits un derwent unilateral anterior cruciate ligament transection(ACLT)and then divided into two groups randomly. 100μmol/L DHEA resolved in the dimethylsulphoxide were injected into the knees of experimental rabbits 4 weeks after transection,once a week for five weeks.Rabbits in the control group were treated under the same schedule using dimethylsulphoxide.All rabbits were killed 9 weeks after ACLT and the knee joints were evalu- ated by gross morphology and histology.The mRNA expression of metalloproteinases-3(MMP-3),tissue in- hibitor of metalloproteinases-1(TIMP-1)and interleukin-lbeta(IL-1β)in the cartilage and synovium was analyzed using reverse transcription polymerase chain reaction(RT-PCR).Results Gross morphologic in- spection and histological evaluation showed that the extent and grade of cartilage and synovium damage in the experimental group were less severe than the control group.The mRNA expression of MMP-3 in cartilage and synovium decreased significantly in the experimental group(both P<0.05).The mRNA expression of TIMP-1 in cartilage and synovium increased significantly in the experimental group compared with that in the control group(both P<0.05).No significant difference of IL-1βmRNA expression in cartilage was found between the experimental and the control groups(P>0.05).The mRNA expression of IL-1βin the synovium was signifi- cantly suppressed in the experimental group compared with that in the control group(P<0.01).Conclusion DHEA protects against cartilage degradation,alleviates synovium inflammation and inhibits the progression of osteoarthritis in the experimental model.Down-regulation of MMP-3 and up-regulation of TIMP-1 in cartilage and synovium and IL-1βin the synovium may be the mechanism of the protective effect of DHEA on os- teoarthritis.
Key concepts: Cartilage, Osteoarthritis, Medicine, Anterior cruciate ligament, Matrix metalloproteinase, Reverse transcription polymerase chain reaction, Dehydroepiandrosterone, Endocrinology