Articular cartilage metabolism in patients with Kashin–Beck Disease: an endemic osteoarthropathy in China

Abstract

The objective of this study was to investigate CD44 and proteoglycan metabolism in patients suffering from Kashin-Beck Disease (KBD), an endemic osteoarthropathy that affects 2.5 million of 30 million people living in the KBD regions of China. Immunohistochemical analyses of cluster of differentiation-44 (CD44), BC-13 and 3-B-3(-) expression were performed in cartilage sections harvested from KBD and normal patients. In addition, the serum levels of soluble CD44 (sCD44), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-1 were determined using a sandwich enzyme linked immunosorbent assay. Hematoxylin & eosin and toluidine blue staining indicated that there was cell necrosis and proteoglycan loss in cartilage from both KBD children and adult cartilage. Strong immunohistochemical staining for CD44, BC-13 and 3-B-3(-) occurred in the majority of adult KBD patients and most KBD children. Furthermore, statistically significant elevated levels of sCD44, IL-1beta and TNF-alpha were found in the sera of both adult and child KBD patients when compared to the levels of normal adult and child controls. Interestingly, IL-1beta and TNF-alpha serum levels were all high in normal children from KBD regions when compared to normal children from non-KBD regions suggesting that unidentified factors (e.g., a genetic predisposition) may protect some people from KBD pathology. Our results demonstrate that altered CD44, IL-1beta and TNF-alpha metabolism occurs in the pathogenesis of KBD and there is an increased aggrecanase-generated proteoglycan loss from KBD adult and child cartilage. These primary metabolic changes are likely to be significant contributing factor causing pathological joint formation and instability that leads to secondary osteoarthritis in KBD patients.