ADAMTS4 or ADAMTS5: Which is the Key Enzyme in the Cartilage Degradation of Osteoarthritis and Kashin-Beck Disease?

Abstract

Background: This study aims to investigate the altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 4（ADAMTS4）and a disintegrin and metalloproteinase with thrombospondin motifs 5（ADAMTS5）in the human articular cartilage between osteoarthritis(OA) and Kashin-Beck disease(KBD) and compare their roles in the cartilage injury. Methods: Articular samples were collected from confirmed OA patients and KBD patients then divided into three groups, and the articular cartilages from the normal donors were used as controls. The morphology，location and expression of ADAMTS4 and ADAMTS5 as well as aggrecan were detected by histochemical staining and immunohistochemical staining. Results: Compared to the control, the number of living cells in OA and KBD groups declined at three zones. Meanwhile, the results of toluidine blue staining showed that there was a loss of aggrecan in extracellular matrix of KBD and OA cartilages. The amounts of chondrocytes positively stained for ADAMTS4 were lower in the middle and deep zones of OA and KBD cartilages than those in the control samples. On the contrary, the immunostaining for ADAMTS5 significantly increased in OA and KBD group compared with control group at all three zones. Notably, although there was no statistical significance, the expression of ADAMST5 in KBD was slightly higher than the ones in OA in superficial, middle and deep zones. Conclusions: The role ADAMTS4 acted in aggrecan degradation was seemingly minor. It could be inferred that ADAMTS5 is the key enzyme in the cartilage destruction, particularly in KBD cartilage, which could explain the complex pathogenesis of KBD and provide a potential therapeutic target for KBD patients.