Aggrecan degradation in osteoarthritis and rheumatoid arthritis

Aggrecan turnover is critically important to maintain extracellular matrix homeostasis in articular cartilage. Cartilage aggrecan metabolism has been studied in chondrocyte cell cultures, cartilage explant cultures, and in whole animal models. In many of these studies, matrix metalloproteinases (MMPs) are proposed to degrade cartilage aggrecan. MMP expression appears elevated in joint tissues from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) (Dean et al. 1989, Wolfe et al. 1993) and inhibitors of both MMPs and thiol proteinases have been shown to block aggrecan (Buttle et al. 1992) and type II collagen (Mort et al. 1993) degradation in cartilage explant cultures. Using antibodies and cDNA probes, elevations in expression and concentration of many of these enzymes in animal models and in OA and RA have been described. Human cartilage aggrecan has now been cloned and sequenced (Doege et al. 1991). This information, in combination with the ability to sequence aggrecan and aggrecan fragments at the protein level, has resulted in the identification of several aggrecan fragments which appear to result from proteinase degradation. In this report, we describe data which suggest that MMPs may in part be responsible for aggrecan catabolism in normal articular cartilage, as well as in the elevated catabolism seen in OA and RA

Monoclonal Antibodies to Skeletal Muscle Cell Surface

About half of the mass of a vertebrate’s body is muscle tissue, of which the principal cell is the muscle fiber: an extremely long, multinucleate cell which has a regionally specialized surface for interaction with tendons, for propagation of action potentials, and for reception of chemical signals from motor neurons. The intimate relation between motor neuron and muscle fiber has been of special importance to neurobiologists. Studies of the neuromuscular junction have provided fundamental information about synaptic communication. Furthermore, evidence of long-term trophic interactions between muscle fibers and motor neurons has been important for the development of ideas about the plasticity and stability of neuronal connections