Yaron M, Shirazi I, Yaron I
Arthritis Research Unit, Department of Rheumatology, Tel Aviv-Sourasky Medical Center, Ichilov Hospital, Israel.
Osteoarthritis Cartilage. 1999 May;7(3):272-80. doi: 10.1053/joca.1998.0201.
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-1beta, nitric oxide (NO) and receptor agonist (IL-1ra) in human OA cartilage and synovial tissue cultures.
Synovial tissue and cartilage derived from OA patients were kept in culture for 48-72 hours in the presence of 1 microg/ml of lipopolysaccharide (LPS) with or without diacerein (10(-7)-10(-5) M), rhein (10(-7)-10(-5) M) and hydrocortisone (5 microg/ml). IL-1beta, IL-1ra, NO productions and 35S uptake were measured in culture media. In some experiments the resulting supernatants from synovial tissue cultures were added to cartilage.
Diacerein and rhein, as well as hydrocortisone, significantly inhibited LPS-induced IL-1beta production by synovial tissue and cartilage. They also significantly reversed the inhibitory effect of LPS on cartilage 35S uptake. Culture media from synovial tissue containing LPS+diacerein (10(-6) M) or +rhein (10(-6) M) 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.
An inhibitory effect of diacerein and rhein at therapeutic concentrations on both IL-1beta 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.
骨关节炎（OA）的病因仍存在争议。已知有几个因素参与关节软骨的破坏。白细胞介素-1（IL-1）在骨关节炎（OA）的发病机制中直接或通过刺激分解代谢因子（如一氧化氮（NO））发挥重要作用。本研究的目的是评估新型抗OA药物双醋瑞因及其活性代谢产物大黄酸对人OA软骨和滑膜组织培养物中IL-1β、一氧化氮（NO）和受体激动剂（IL-1ra）的产生及功能的影响。
将OA患者的滑膜组织和软骨在含有1微克/毫升脂多糖（LPS）的情况下培养48 - 72小时，同时添加或不添加双醋瑞因（10⁻⁷ - 10⁻⁵M）、大黄酸（10⁻⁷ - 10⁻⁵M）和氢化可的松（5微克/毫升）。在培养基中测量IL-1β、IL-1ra、NO的产生以及³⁵S摄取。在一些实验中，将滑膜组织培养产生的上清液添加到软骨中。
双醋瑞因、大黄酸以及氢化可的松均显著抑制LPS诱导的滑膜组织和软骨中IL-1β的产生。它们还显著逆转了LPS对软骨³⁵S摄取的抑制作用。含有LPS + 双醋瑞因（10⁻⁶M）或 + 大黄酸（10⁻⁶M）的滑膜组织培养基对软骨合成的抑制作用明显小于仅含LPS的培养基。双醋瑞因和大黄酸降低了滑膜组织和软骨培养基中NO的释放，并提高了软骨培养基中IL-1ra的水平。
提示治疗浓度的双醋瑞因和大黄酸对人滑膜组织和软骨中IL-1β的分泌及功能具有抑制作用。双醋瑞因和大黄酸对LPS刺激的OA滑膜组织和软骨中NO产生的影响可能共同促成并阐明了它们的抗OA特性。
