EAnti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures

Abstract

Objective: The etiology of osteoarthritis (OA) is still a matter of debate. Several factors are known to be involved in the destruction of the articular cartilage. Interleukin-1 (IL-1) plays an important role in the pathogenesis of osteoarthritis (OA) either directly or through the stimulation of catabolic factors, such as nitric oxide (NO). The objective of this study was to evaluate the effect of diacerein, a new anti-OA agent and its active metabolite, rhein, on the production and function of IL-1β, nitric oxide (NO) and receptor agonist (IL-1ra) in human OA cartilage and synovial tissue cultures.Design: Synovial tissue and cartilage derived from OA patients were kept in culture for 48–72 hours in the presence of 1μg/ml of lipopolysaccharide (LPS) with or without diacerein (10−7–10−5M), rhein (10−7–10−5M) and hydrocortisone (5μg/ml). IL-1β, IL-1ra, NO productions and35S uptake were measured in culture media. In some experiments the resulting supernatants from synovial tissue cultures were added to cartilage.Results: Diacerein and rhein, as well as hydrocortisone, significantly inhibited LPS-induced IL-1β production by synovial tissue and cartilage. They also significantly reversed the inhibitory effect of LPS on cartilage35S uptake. Culture media from synovial tissue containing LPS+diacerein (10−6M) or +rhein (10−6M) had a significantly less inhibitory effect on cartilage synthesis than culture media containing LPS only. Diacerein and rhein decreased NO release in synovial tissue and cartilage media and increased IL-1ra levels in cartilage culture media.Conclusion: An inhibitory effect of diacerein and rhein at therapeutic concentrations on both IL-1β secretion and function in human synovial tissue and cartilage is suggested. Diacerein and rhein effects on NO production by LPS-stimulated OA synovial tissue and cartilage may both contribute and elucidate their anti-OA properties.