The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules

Abstract

Chondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant. In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico-chemical properties of cartilage-specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage-specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage-specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints.

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

“…Downstream upregulation of the Sox9 transactivation target Col2a1 [39,40] was also confirmed in transplanted oim compared to oim controls (0.11 -0.01$2 -DCt vs. 0.04 -0.01$2 -DCt respectively, P < 0.05) and of the key cartilage matrix component aggrecan [41,42] (4.8 -0.8$2 -DCt vs. 1.1 -0.4$2 -DCt respectively, P < 0.01), found in proliferating chondrocytes. However, expression of the Sox9 target gene Pthrp, which inhibits chondrocyte maturation [43][44][45], was similar in transplanted and nontransplanted oim (5.2 · 10 -4 -0.7 · 10 -4 $2 -DCt vs. 4.8 · 10 -4 -0.5 · 10 -4 $2 -DCt ).…”

Chondrogenic differentiation of bovine bone marrow mesenchymal stem cells (MSCs) in different hydrogels: Influence of collagen type II extracellular matrix on MSC chondrogenesis

“…In addition to these macromolecules, collagen types VI, IX, XI; decorin; biglycan, cartilage oligomeric matrix protein (COMP); and fibromodulin are also present in minor concentrations (Muir, 1995;Poole et al, 2001). It is well known that damaged articular cartilage has poor intrinsic regenerative capacity.…”

Mechanical Regulation of Mitogen-activated Protein Kinase Signaling in Articular Cartilage

“…Articular cartilage serves as a bearing surface for joints (1,2). In this capacity, it is routinely exposed to mechanical loading.…”

“…Articular cartilage biosynthetic activity is also regulated by cell signaling molecules. Insulin-like growth factor-I (IGF-I) 1 is the predominant anabolic growth factor in synovial fluid (20) and stimulates the synthesis of both proteoglycans and collagen (21). Although static compression reduces cartilage IGF-I content (22), the short time course of inhibition of cartilage biosynthesis by static compression is not consistent with an effect that is mediated entirely by IGF-I or other soluble growth factors.…”