P159 ARTICULAR CARTILAGE CATABOLISM IN THE PATHOGENESIS OF KASHIN-BECK DISEASE

Abstract

Purpose: Kashin-Beck Disease (KBD) is an endemic, chronic, degenerative osteoarthropathy which affects 2.5 million of 30 million people living in the KBD region of China. The symptoms include joint pain, stiffness of the joints after getting up in the morning, disturbances of flexion and extension in the elbows, enlarged phalangeal joints and limited motion in the middlesized and large joints of the body. It manifests as cartilage degeneration and necrosis, with pathological changes occurring in growth plate and articular cartilage. At present the etiology and pathogenesis of KBD is unclear. One of the most popular hypotheses is that KBD is caused by mycotoxins. The other etiologies include selenium deficiency in soil and water in KBD area, nutrition deficiency and virus infection etc. However, all of the hypotheses lack adequate experimental evidence to support any particular conclusion. This study investigated the extracellular matrix metabolism in cartilage and serum levels of IL-1 beta, TNF-alpha, MMP-1 and CD44 in serum of KBD patients. Methods: Immunohistochemical analyses of normal and KBD patient cartilage (16 adults and 4 children and normal agematched patient tissue 4 adults and 3 children) was performed using a monoclonal antibody recognising CD44, the IGD aggrecase-generated neoepitope (monoclonal antibody BC13 recognising ... EGE373) and monoclonal antibody 3-B-3(-) which recognizes thee nonreducing terminal of CS chains in osteoarthritic cartilage. In addition, the serum levels of soluble CD44 (sCD44), IL-1 beta, TNF-alpha and MMP-1 were determined in KBD patients (20 adults and 18 children) and normal patients (20 adults and 18 children) using a competitive ELISA. Results: Toluidine Blue and Saffron O staining indicated there was a proteoglycan loss in both of KBD children and adult cartilage. Strong immunohistochemical staining for CD44 occurred in 14 of 16 adult KBD patients with moderate staining present in the remaining two patients. Similarly, strong CD44 immunostaining occurred in 3 of the 4 KBD children with moderate staining in the fourth KBD child. In contrast, weak CD44 immunostaining was only found in two of the four normal adult cartilage and none of the three normal child samples. Immunohistochemical staining with MAb BC-13 and 3-B-3(-) showed an intensive staining in both of KBD children and adult cartilage when compared with the normal cartilage samples. Furthermore, statistically significant elevated levels of sCD44, IL-1 beta and TNF-alpha were found in the sera of both adult and child KBD patients when compared to serum levels of normal adult and child controls. However, there was no difference in MMP-1 level between KBD and normal children. Conclusions: Our results demonstrate that altered IL-1 beta, TNF-alpha, aggrecan and CD44 metabolism occurs in the pathogenesis of KBD and there is an increased aggrecanasegenerated proteoglycan loss from KBD adult and children cartilage. These primary metabolic changes are a contributing factor causing pathology in joint formation and instability which in turn leads to the onset of secondary osteoarthropathy in the major load-bearing joints of KBD patients. P160