Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts

Cartilage oligomeric matrix protein has been implicated as an important com ponent of endochondral ossification because of its direct effects on chondr ocytes. The importance of this protein for skeletal development and growth has been recently illustrated by the identification of mutations in cartila ge oligomeric protein genes in two types of inherited chondrodysplasias and osteoarthritic phenotypes: multiple epiphyseal dysplasia and pseudoachondr oplasia. In the present study, we report the presence of cartilage oligomer ic protein in embryonic and adult osteoblasts. A foot from a 21-week-old hu man fetus, subchondral bone obtained from knee replacement surgery in an ad ult patient, and a limb from a 19-day-postcoital mouse embryo were analyzed with immunostaining and in situ hybridization. In the human fetal foot, ca rtilage oligomeric protein was localized to osteoblasts of the bone collar and at the newly formed bone at the growth plate and bone diaphyses. Immuno staining was performed on the adult subchondral bone and showed positive in tracellular staining for cartilage oligomer ic protein of the osteoblasts l ining the trabecular bone. There was no staining of the osteocytes. Immunos taining of the mouse limb showed the most intense staining for cartilage ol igomeric protein in the hypertrophic chondrocytes and in the surrounding os teoblast cells of the developing bone. Cartilage oligomeric protein mRNA an d protein were detected in an osteoblast cell line (MG-63), and cartilage o ligomeric protein mRNA was detected from human cancellous bone RNA. These r esults suggest that the altered structure of cartilage oligomeric protein b y the mutations seen in pseudoachondroplasia and multiple epiphyseal dyspla sia may have direct effects on osteoblasts, contributing to the pathogenesi s of these genetic disorders.