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Abstract

CILP = cartilage intermediate-layer protein; CMP = cartilage matrix protein; COMP = cartilage oligomeric matrix protein; CS = chondroitin sulfate; CS1/CS2 = chondroitin-sulfate-attachment regions of aggrecan; G1/G2/G3 = globular regions [of aggrecan]; IL-1 = interleukin-1; PRELP = proline-and arginine-rich end leucine-rich repeat protein; SLRP = small leucine-rich repeat proteoglycan.Available online http://arthritis-research.com/content/3/6/342 IntroductionThe extracellular matrix of articular cartilage contains a large variety of noncollagenous proteins. Many of these are listed in Table 1, and while this list is by no means exhaustive, it does include those that have been studied in the most detail. It is impossible to give any common feature that unites this group of molecules, as they vary greatly in structure and function, and in some cases it is not clear that they are even made by the chondrocytes. Many of the molecules are proteoglycans, bearing glycosaminoglycan chains, whereas others are glycoproteins or even nonglycosylated proteins. Some of the molecules represent degradation products of larger precursors that accumulate because of their interaction with other matrix components. Many of the molecules play a structural role, whereas others may be involved in regulating cell function. In addition, many of the molecules vary in their abundance and structure with anatomical site or the person's age, and many are not unique to cartilage. The importance of many of the molecules to cartilage function is illustrated in Table 2, which shows their association with pathology when they are produced in a mutant form. Proteoglycans of the cartilage extracellular matrix Aggregating proteoglycansAmong the noncollagenous proteins of cartilage, aggrecan has undoubtedly received the greatest attention, because of its high abundance in cartilage, its close association with the ability of the tissue to resist compression, and its modification in many cartilage disorders. Aggrecan belongs to the family of aggregating proteoglycans that form large, multimolecular complexes with hyaluronan AbstractCartilage contains numerous noncollagenous proteins in its extracellular matrix, including proteoglycans. At least 40 such molecules have been identified, differing greatly in structure, distribution, and function. Some are present in only selected cartilages or cartilage zones, some vary in their presence with a person's development and age, and others are more universal in their expression. Some may not even be made by the chondrocytes, but may arise by absorption from the synovial fluid. In many cases, the molecules' function is unclear, but the importance of others is illustrated by their involvement in genetic disorders. This review provides a selective survey of these molecules and discusses their structure, function, and involvement in inherited and arthritic disorders.

The Role of Human HtrA1 in Arthritic Disease

“…Destruction of articular cartilage is a common feature of OA and RA (9,10). We identified the extracellular matrix glycoprotein fibronectin as a natural substrate of HtrA1, suggesting a direct role of HtrA1 in matrix degradation.…”

“…Progressive degradation of components of the extracellular matrix plays an important role in the pathogenesis of arthritic diseases (9,10). The destruction of the major cartilage components is driven by members of all classes of proteases, including serine proteases, although the matrix metalloproteases (MMPs) are considered to be the primary instigators (11)(12)(13).…”

Synthesis rates and binding kinetics of matrix products in engineered cartilage constructs using chondrocyte-seeded agarose gels

“…This observation suggests that TGF-β3 primes the chondrocytes for greater collagen synthesis but is not needed continuously, as chondrocytes retain a memory of this exposure; similar behavior has been observed in fibroblasts (Varga et al, 1987). Both supplementation groups also have a high retention ratio (Figure 5) potentially due to TGF-β3 upregulating small PGs, such as decorin and fibromodulin (Burton-Wurster et al, 2003; Roughley, 2001). Prior studies have analyzed the binding of PGs with collagen (Obrink, 1973a, b; Obrink et al, 1975); specifically, K d of the collagen-PG interaction is on the order of 30 – 1000 nM under low osmotic conditions (Obrink et al, 1975).…”

“…Pyridinoline cross-links between collagen fibrils act to retain and strengthen the PG-collagen network (Eyre and Wu, 2005; Williamson et al, 2003a; Williamson et al, 2003b). In addition, cartilage oligomeric matrix protein (COMP) is a high molecular weight (~500 kDa) matrix protein that may play a structural role in cartilage given its concentration (0.4% ww) in the tissue and binding affinity for both PGs and type II collagen (Chen et al, 2007; DiCesare et al, 1996; Hedbom et al, 1992; Rosenberg et al, 1998; Roughley, 2001). …”

Sanmiao formula inhibits chondrocyte apoptosis and cartilage matrix degradation in a rat model of osteoarthritis

“…The stability of articular cartilage depends on the biosynthetic activities of chondrocytes, which synthesize appropriate ECM molecules to maintain cartilage homeostasis (2,3). Chondrocyte apoptosis alters the cartilage matrix synthesis, leading to matrix degeneration and destruction, and finally to OA (4).…”