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

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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.