The levels of the primary lubricating macromolecule in synovial fluid, proteoglycan 4 has also been reported to be higher in the synovial fluid samples of patients in the advanced stage of OA. Proteins not reported in OA synovial fluid Out of 677 proteins identified, 545 thenthereby have not been re ported earlier in OA synovial fluid. A partial list of Inhibitors,Modulators,Libraries novel proteins is provided in Table 2. Some of the novel mole cules identified are discussed below. Representative MS MS spectra of peptides identified from the proteins, Nidogen 2, Alanyl aminopeptidase, Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 and Osteoglycin are shown in Figure 3. Extracellular Inhibitors,Modulators,Libraries matrix proteins Degradation of the articular cartilage is a hallmark of OA.

Damage to the cartilage causes irreversible changes in the ECM that Inhibitors,Modulators,Libraries results in joint dysfunction. Asporin is an ECM protein that belongs to the small leucine rich proteoglycan family. Asporin was detected at higher levels in articular cartilage, subchondral bone and Inhibitors,Modulators,Libraries osteophytes of OA patients. A recent study dem onstrated that the expression of ASPN was highly regu lated by the transcription factor, SP1 in the human articular chondrocytes. Asporin has been shown to induce osteoblast driven collagen mineralization. Polymorphisms in the aspartic acid repeat of ASPN have been shown to be associated significantly with the suscep tibility to OA. Also, it has been shown to regulate chondrogenesis by inhibiting TGF beta 1 mediated ex pression of genes, aggrecan and type II collagen in the cartilage.

NID2 is a basement membrane protein that has been shown to interact with collagen type I, IV, laminin 1 and perlecan present in the ECM. Kreugel J et al, have shown that NID2 expres sion was increased in late stage OA cartilage in humans and established Inhibitors,Modulators,Libraries its role in cartilage regeneration. Proteolytic enzymes and protease inhibitors Degradation of the ECM in OA synovial joint has been shown to be primarily catalyzed by the proteolytic en zymes. Alterations in the activities and expression levels of these enzymes and their associated inhibitors have been shown to disturb the balance between anabolism and catabolism in the affected joints. Alanyl aminopeptidase is a membrane bound metalloprotease enzyme expressed on the surface of hu man normal and malignant myeloid cells, fibroblasts, he patocytes and epithelial cells of the kidney and small intestine.

It has also been more shown to be expressed by vascular endothelial cells and played a significant role in angiogenesis. It has been suggested that simultan eous inhibition of ANPEP and dipeptidyl peptidase 4 would provide an effective means of therapy against T cell mediated disorders including autoimmune diseases, inflammation and allergy. Recent studies have spec ulated its role in inflammatory monocyte trafficking. ADAM like, decysin 1 is a recently identified member of the disintegrin metalloproteinase family.