CARTILAGE-SPECIFIC OVEREXPRESSION OF C-PROPEPTIDE OF TYPE II COLLAGEN AFFECTED MATRIX MINERALIZATION IN TRANSGENIC MICE

Abstract

The C-propeptide of type II collagen (CppII) is cleaved from the procollagen molecule at the time of extracellular secretion from chondrocytes, and was reported to localize in the lower hypertrophic zone of the growth plate cartilage. In the present study, the in vivo role of CppII in the process of endochondral bone formation was investigated by cartilage-specific overexpression of CppII in transgenic mice. Two independent lines of transgenic mice were obtained and they showed mild skeletal dysplasia, as evidenced by morphometric measurement of skeletal bones. Whole body staining revealed delayed mineralization of embryonic endochondral bones, including occipital bone and vertebral bodies. Histological sections showed reduced area of mineralization and scattered chondrocyte hypertrophy in the lower part of growth plate cartilage in the embryonic long bones. Immuno-electron micrographs demonstrated that CppII co-localized with collagen fibrils in the extracellular matrix of the cartilage. Taken together, these results indicate that overexpression of CppII affected endochondral bone formation by negatively regulating the matrix mineralization.