Effect Of Dehydroepiandrosterone On MRNA Expression Of ADAMTS-4, ADAMTS-5 And TIMP-3 In The Cartilage Of Rabbits With Osteoarthritis

Objective.To observe the effect of intra-articular injection of dehydroepiandrosterone(DHEA) on mRNA expression of aggrecanase-1(ADAMTS-4),aggrecanase-2(ADAMTS-5),and tissue inhibitor of metalloproteinases-3(TIMP-3) in the cartilage of rabbits with osteoarthritis.Methods.Ten New Zealand rabbits underwent bilateral anterior cruciate ligament transection (ACLT).On the basis of randomization one knee of each rabbit was treated with 100μmol / L DHEA resolved in the dimethylsulphoxide(experimental group) and the other knee was treated under the same schedule using dimethylsulphoxide(control group) 4 weeks after transection, once a week for eight weeks.Twelve weeks after ACLT all rabbits were killed and the knee joints were evaluated by gross morphology.The mRNA expression of ADAMTS-4, ADAMTS-5 and TIMP-3 in the cartilage was analyzed using reverse transcription polymerase chain reaction(RT-PCR).Results.Gross morphologic inspection showed that the extent of cartilage damage in the experimental group was less severe than in the control group.The mRNA expression of ADAMTS-4 and ADAMTS-5 in cartilage decreased significantly in the experimental group(P<0.01;P<0.05).The mRNA expression of TIMP-3 in cartilage increased significantly in the experimental group compared with that in the control group(P<0.01).Conclusion.DHEA protects against cartilage degradation and inhibits the progression of osteoarthritis in the experimental model.Down-regulation of ADAMTS-4,ADAMTS-5 and up-regulation of TIMP-3 in cartilage may be the mechanism of the protective effect of DHEA on osteoarthritis.