Variation patterns of two degradation enzyme systems in articular cartilage in different stages of osteoarthritis: Regulation by dehydroepiandrosterone

Abstract

Background Osteoarthritis (OA) is a multifactorial degenerative joint disease in which the cartilaginous matrix of the articular joint is destroyed in a continuous process. We evaluated mRNA levels of cysteine proteinases/cystatin C system and urokinase plasminogen activator/plasminogen activator inhibitor-1 (uPA/PAI-1) system in articular cartilage and regulation by dehydroepiandrosterone (DHEA) in different stages of osteoarthritis (OA). Methods One hundred and eight rabbits underwent anterior cruciate ligament transection (ACLT) in the left knee, 54 received weekly intra-articular injections of DHEA (100 µmol/l) 0.3 ml 3 weeks after transaction as DHEA group. Thirty-six rabbits (18 from 2 groups respectively) were euthanized 6, 9, and 12 weeks after ACLT. All left knee joints were assessed by gross morphology and histology, meantime the gene expression from articular cartilage was analyzed. Results Cathepsins and uPA gene increased significantly 6 weeks and reached peak in the 9th week, while declined to extremely low levels 12 weeks after ACLT. Cystatin C decreased accompanied by OA progression, while PAI-1 expressed in the same trend with uPA. Additionally, these 2 enzyme systems were markedly suppressed by DHEA 6 and 9 weeks after ACLT but not in the 12th week. Conclusion The variation of these 2 enzyme systems was closely related to the progression of OA, and could be regulated by DHEA especially in the early and medium stages of OA.