Expression and activity of ADAMTS-5 in synovium

ADAMTS proteinases, belonging to the adamalysin subfamily of metalloprotein ases, have been implicated in a variety of cellular events such as morphoge nesis, cell migration, angiogenesis, ovulation and extracellular matrix bre akdown. Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) have been ide ntified in cartilage and are largely responsible for cartilage aggrecan bre akdown. We have shown previously that synovium, the membrane lining diarthr odial joints, generates soluble aggrecanase activity. We report here the ex pression, localization and activity of ADAMTS-5 from human arthritic and bo vine synovium. ADAMTS-5 was expressed constitutively in synovium with littl e or no transcriptional regulation by recombinant human interleukin-1 alpha or all-trans-retinoate, factors previously shown to upregulate aggrecanase activity in cartilage. Aggrecanase activity generated by synovium in vitro and recombinant ADAMTS-5 cleaved aggrecan extensively, resulting in aggrec an fragments similar to those generated by chondrocyte-derived aggrecanases , and the activity was inhibited by heparin. ADAMTS-5 was immunolocalized i n human arthritic synovium, where staining was mostly pericellular, particu larly in the synovial lining and around blood vessels; some matrix staining was also seen. The possibility that synovium-derived ADAMTS-5 may play a r ole in cartilage aggrecan breakdown is discussed.