Orthodontic treatments of skeletal malocclusions rely on influencing growth of the mandibular condyle, however, the biological mechanisms by which the condylar cartilage responds to treatment remain elusive. The mandibular condylar (MC) cartilage is a secondary type cartilage containing Type I and Type II collagens. Based on these data, MC cartilage has been hypothesized to contain, a progenitor cell (skeleto-blast) capable of modulating its phenotypic expression between cartilage and bone. Local biomechanical factors in vivo can shift its synthetic pathway from Type I to Type II collagen. The proposed experiments will characterize the MC cartilage phenotype with respect to two small extracellular matrix proteins, matrix tau-carboxyglutamic acid (Gla) protein (MGP) and osteocalcin (or bone Gla protein, BGP). MGP and BGP are similar in that they contain the vitamin K- dependent Ca2+-binding amino acid Gla and have 20% sequence identity; yet they are very different in that MGP is water-insoluble and is anchored to the organic matrix of bone and cartilage, while BGP is water-soluble and bone-specific. The proposed studies will test the hypothesis that both MGP and BGP mRNA are present in MC cartilage, a primary cartilage, was previously shown to express MGP but not BGP. MGP and BGP will be measured in relation to other phenotypic markers of cartilage and bone (Type I, II collagens and alkaline phosphatase). Finally, the feasibility of studying their synthesis in MC and NS chondrocyte cell cultures will be to test the effects of mechanical tension in vitro with a Flexercell Strain Instrument. These studies will contribute to the understanding of the temporal changes in the extracellular matrix of the mandibular condyle which are relevant to clinical problems such as skeletal malocclusions, craniofacial anomalies and temporomandibular joint disorders.
