Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging

Objective: Interleukin-6 (IL-6) is expressed in osteoarthritic joints but its function in osteoarthritis (OA) is unknown. To study this, spontaneous and experimental OA were evaluated in IL-6 deficient (IL-6(-1-)) mice. Design: Histology of knees of 18-23-month-old wild type (wt) and IL-6(-1-) mice was compared for signs of OA. Cartilage proteoglycan (PG) density was measured by image analysis on safranin-O stained whole knee sections. Chondrocyte PG synthesis was measured ex vivo by S-35-sulfate incorporation. Knee bone mineral density (BMD) was measured by dual energy x-ray absorptiometry. In young mice (3 months), OA was induced by intra-articular injection of collagenase. Results: The incidence of extensive cartilage loss at both lateral and medial sides was markedly higher in old IL-6(-1-) males, but not in females, as compared to their wt controls. Compared to age-matched wt mice, reduced ex vivo PG synthesis was found during aging in IL-6(-/-) males, without affecting their cartilage PG density. IL-6(-1-) males showed more extensive extracellular matrix deposition in the collateral ligaments and subchondral bone sclerosis, predominantly at the medial side. Total knee BMD decreased more in IL-6(-1-) (-23%) than in wt (-10%) males during aging. Collagenase-induced CA showed a similar degree of joint pathology in both strains, implying that OA susceptibility was not different at younger age. Conclusions: Upon aging, IL-6(-1-) male mice developed more severe spontaneous OA. Reduced PG synthesis and BMD values might be indicative for an impaired repair response in IL-6(-1-) mice. This suggests a protective role for IL-6 in age-related OA in male mice. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.