IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage

Elevated concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor ( sIL-6R) in the synovial fluids and serum of patients with arthritis have be en implicated in the joint tissue destruction associated with these conditi ons, however studies conducted to date on the role and effects of IL-6 in t he process of cartilage proteoglycan (aggrecan) catabolism are disparate. I n the present study, bovine articular cartilage explants were maintained in a model organ culture system in the presence or absence of IL-1 alpha or T NF-alpha, and under co-stimulation with or without IL-6 and/or sIL-6R. Afte r measuring proteoglycan loss from the explants, the proteolytic activity a nd expression profiles of aggrecanase(s) was assessed for each culture cond ition. Stimulation of cartilage explants with IL-6 and/or sIL-6R potentiate d aggrecan catabolism and release above that seen in the presence of IL-1 a lpha or TNF-alpha alone. This catabolism was associated with aggrecanase (b ut not MMP) activity, with correlative mRNA expression for aggrecanase-2. ( C) 2000 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.