New Insights into Joint Cartilage Degeneration and Synovitis in Rheumatoid Arthritis and Osteoarthritis. - Effects of Adrenomedullin-

风湿性关节炎患者血浆肾上腺髓质素及PAMP水平约为正常水平的2倍，且肾上腺髓质素与血浆及关节液中肾上腺髓质素含量相等。风湿性关节炎患者关节组织中滑膜的肾上腺髓质素含量高于韧带组织和半月板。这些证据提示肾上腺髓质素在体内可能主要作为激素起作用，并提示肾上腺髓质素的活动方式主要在滑膜内。在风湿性关节炎的滑膜中，证实了肾上腺髓质素和PAMP基因的表达，并在培养的滑膜中组成分泌。此外，肾上腺髓质素还能显著抑制IL - 6的分泌。结果表明，肾上腺髓质素在炎性滑膜中的作用具有显著的抗炎作用。当肾上腺髓质素对关节炎具有抗炎作用时，在兔佐剂关节炎模型中，肾上腺髓质素在肿胀关节内注射后5天肿胀减轻，淋巴细胞数量减少，纤维改变促进。因此，证实肾上腺髓质素在风湿性关节炎中具有调节关节炎的作用。此外，正常关节软骨细胞胞浆内大量储存肾上腺髓质素颗粒。在原代培养的软骨细胞中，肾上腺髓质素以剂量依赖的方式诱导细胞凋亡和坏死，并明确其作为局部调节因子在关节炎中细胞增殖的效率。

The plasma adrenomedullin and PAMP level was about twice higher than the normal level in the patient with rheumatic arthritis, in addition, adrenomedullin equal with the concentration which was included in the plasma and in the joint fluid. Synovia has higher amount of adrenomedullin than ligamentous tissues and meniscus in the joint tissues in the patient with rheumatic arthritis. These evidences lead to us the possibility of adrenomedullin acting chiefly as a hormone in vivo and suggestion of the fashion of the adrenomedullin activity mainly in synovia.In the synovia with the rheumatic arthritis, the gene expression of adrenomedullin and PAMP is confirmed, and these were composed secretion in the cultured the synovia. Moreover, the secretion of IL - 6 was significantly inhibited in addition with adrenomedullin. It was clarified that there was a significant anti-inflammatory effect in the role of adrenomedullin in the inflammatory synovium.When adrenomedullin was administered by using an anti-inflammatory effect in arthritis, in using the rabbit adjuvant arthritis model, adrenomedullin caused the reduce of the swelling, decreasing the number of the lymphocytes and promotion of fibrous change in five days after it had treated with injection into a swollen joint. Therefore, it was proven that adrenomedullin had a role as the regulator for arthritis in rheumatic arthritis.In addition normal joint chondrocytes voluminously stored adrenomedullin in the granules in its cytoplasm. In the primary cultured chondrocytes, adrenomedullin induced cell apoptosis and necrosis as a dose depended manner, and the efficiency was clarified for the cell proliferation as a local regulator in the arthritis.