Cartilage oligomeric matrix protein is a non-collagenous
extracellular matrix protein expressed primarily in cartilage, ligament, and tendon.
Cartilage oligomeric matrix protein has been studied extensively because mutations in the gene cause two skeletal dysplasias,
pseudoachondroplasia and
multiple epiphyseal dysplasia.
Pseudoachondroplasia is a disproportionate dwarfing condition associated with joint abnormalities, while
multiple epiphyseal dysplasia is less severe. Both of these skeletal dysplasias have a characteristic chondrocyte pathology that consists of intracellular retention of
cartilage oligomeric matrix protein and other
extracellular matrix proteins in an enlarged rough endoplasmic reticulum. This toxic intracellular retention of
extracellular matrix proteins causes chondrocyte cell death thereby decreasing linear bone growth. Additionally, when
cartilage oligomeric matrix protein and the other co-retained
proteins are not exported to the extracellular matrix, the resulting matrix is abnormal and easily erodes with normal physical activity.
Cartilage oligomeric matrix protein is also a marker for joint destruction associated
osteoarthritis,
rheumatoid arthritis, joint
trauma, and intense activity. Serum
cartilage oligomeric matrix protein levels are higher in aggressive cases of
arthritis and levels are used to predict future
disease progression. Recent studies have identified molecular functions of
cartilage oligomeric matrix protein that may contribute to its role in skeletal disease. These molecular functions include: binding other ECM
proteins, catalyzing polymerization of
type II collagen fibrils, and regulation of chondrocyte proliferation. Here, we review
cartilage oligomeric matrix protein's role in skeletal disease and potential molecular mechanisms.