Relapsing polychondritis is a systemic disease associated with a destruction of cartilage in various parts of the body. Sera from six patients with relapsing polychondritis and one patient with microscopic polyarteritis nodosa as well as from six controls were analyzed by immunoblotting and ELISA. All patients had autoantibodies against native collagens II and IX. The serum from one patient showed a strong reaction with all three collagen chains of the high molecular weight fraction of collagen IX after denaturation; sera from four patients showed autoantibodies against alpha 2 (XI) and sera from three patients showed autoantibodies against the covalently cross-linked gamma component of collagen XI. The presence of autoantibodies against collagens II, IX, and XI, which form the major fibrillar scaffold in cartilage and mediate the interaction of collagen fibrils and proteoglycan, suggests that autoantibodies against cartilaginous collagen may play a crucial role in the pathogenesis of relapsing polychondritis and microscopic polyarteritis nodosa.

Collagen I1 was isolated and characterized from hyaline cartilage (articular cartilage) and fibrocartilage (annulus fibrosus). Collagen I1 from the latter tissue has a substantially higher degree of hydroxylation and glycosylation than that isolated from articular cartilage. The higher degree of posttranslational modification was associated with a slower electrophoretic mobility, a greater resistance to mammalian collagenase digestion and a higher thermal stability. An increase of glycosylation accelerates the initial steps in fibril formation of collagen molecules but slows down the following lateral growth. The newly formed aggregates of collagen I1 from annulus fibrosus consisted of fibrils with a smaller diameter.Based on its histological appearance, cartilage is classified into three tissue entities, i. e. hyaline, elastic and fibrocartilage. Hyaline cartilage covers the articular surface of bone and supports the tracheal tubes, larynx and ventral ends of the ribs. Fibrocartilage is a transitional form between hyaline cartilage and fibrous connective tissue. It occurs in the menisci of joints, in the annulus fibrosus of intervertebral discs and in the attachment sites of tendons onto the bones [l]. Collagen, the main structural protein in both tissues, exhibits a high degree of organization based on fibrillar aggregates.Several factors have been suggested to play a role in the control of fibrillogenesis, such as the presence of proteoglycans [2], the mode of procollagen processing [3], the interaction of different collagen types [4] and non-collagenous proteins including integrins p]. Furthermore, experimental evidence showed that the posttranslational modification of collagen molecules plays a crucial role in the stability of individual molecules as well as the stabilization of collagen fibrils. Specifically, hydroxylation of prolyl residues determines the thermal stability of the triple helix of collagen molecules. Hydroxylation of lysyl residues contributes to the crosslinking of collagen molecules which, in turn, contributes to the biomechanical strength of collagen fibrils [6]. Recent circumstantial evidence provides further support that glycosylation of hydroxylysyl residues may regulate the diameter of collagen fibrils [7, 81. In this study, an approach was made to compare collagen I1 from hyaline cartilage (articular cartilage) and fibrocartilage (annulus fibrosus). The analysis showed that the collagen I1 from annulus fibrosus (AFII) has a substantially higher level of hydroxylation and glycosylation than the collagen I1 from articular cartilage (ACII). In order to clarify the influ- ence of different levels of posttranslational modification on the nature of collagen I1 molecules, their electrophoretic migration, thermal stability and susceptibility to mammalian collagenase were investigated. Additionally, we studied the impact of the varying pattern of collagen I1 modifications on the dynamics of the self-assembly and the structure of the fibrils formed in vitro. MATERIALS AND METHODS Extractio...

We conducted in vitro and in vivo assays in a selenium-deficient system to determine if organic matter (mainly fulvic acid; FA) is involved in a free radical mechanism of action for Kashin-Beck disease. Cartilage cell culture experiments indicated that the oxy or hydroxy functional groups in FA may interfere with the cell membrane and result in enhancement of lipid peroxidation. Experiments with rats demonstrated that toxicity from FA was reduced when the hydroxy group was blocked. Induction of lipid peroxidation by FA in liver and blood of rats was similar to that exhibited by acetyl phenyl hydrazine. FA accumulated in bone and cartilage, where selenium rarely concentrates. In addition, selenium supplementation in rats' drinking water inhibited the generation of oxy-free radicals in bone. We hypothesized that FA in drinking water is an etiological factor of Kashin-Beck disease and that the mechanism of action involves the oxy and hydroxy groups in FA for the generation of free radicals. Selenium was confirmed to be a preventive factor for Kashin-Beck disease.ImagesFigure 1Figure 2Figure 3

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