Human Chondrocyte Cultures as Models of Cartilage-Specific Gene Regulation

互联网2014-02-13

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The mature articular chondrocyte embedded in the cartilage matrix is a resting cell with no detectable mitotic activity and a very low synthetic activity (1 ). The markers of mature articular chondrocytes are type II collagen (COL2A1), other cartilage-specific collagens IX (COL9) and XI (COL11), the large aggregating proteoglycan aggrecan, and link protein (see Table 1 ). Chondrocytes also synthesize a number of small proteoglycans such as biglycan and decorin and other specific and nonspecific matrix proteins both in vivo and in vitro. As the single cellular constituent of adult articular cartilage, chondrocytes are responsible for maintaining the cartilage matrix in a low turnover state of equilibrium. In mature cartilage, the chondrocytes synthesize matrix components very slowly. The turnover of collagen in normal adult articular cartilage has been estimated to occur with a half-life of longer than 100 yr (2 ,3 ) and the half-life of aggrecan subfractions is in the range of 3-24 yr, whereas the glycosaminoglycan constituents on the aggrecan core protein are more readily replaced (4 ). Furthermore, normal chondrocyte metabolism in situ occurs in low oxygen tension and is remote from a vascular supply. Thus, it is not surprising that changes in expression of these cartilage matrix constituents occur when the chondrocytes are isolated and placed in monolayer culture, where they increase synthetic activity by several orders of magnitude.

Table 1 Proteins Synthesized by Mature Chondrocytes

Collagens
Type II
Type IX
Type XI
Type VI
Types XII, XIV

Proteoglycans
Aggrecan
Versican
Link protein
Biglycan (DS-PGI)
Decorin (DS-PGII)
Epiphycan (DS-PGIII)
Fibromodulin
Lumican
PRELP (proline/arginine-rich and leucine-rich repeat protein)
Chondroadherin
Perlecan
Lubricin (SZP)

Other noncollagenous proteins (structural)
Cartilage oligomeric matrix protein (COMP; thrombospondin-5)
Thrombospondin-1 and -3
Cartilage matrix protein (matrilin-1); matrilin-3
Fibronectin
Tenascin-c
Cartilage intermediate layer protein (CILP)
Fibrillin
Elastin

Other noncollagenous proteins (regulatory)
S-100
Chondromodulin-I (SCGP) and -II
Glycoprotein (gp)-39,YKL-40
Matrix Gla protein (MGP)
CD-RAP (cartilage-derived retinoic acid-sensitive protein)
Growth factors

Membrane-associate proteins
Integrins (α1β1, α2β1, α3β1, α5β1, α6β1, α10β1, αvβ3, αvβ5)
Anchorin CII (annexin V)
CD44
Syndecan-3

The collagens, proteoglycans, and other noncollagenous proteins in the cartilage matrix are synthesized by chondrocytes at different stages during development and growth of cartilage and the mature articular chondrocyte may have a limited capacity to maintain and repair some of the matrix components, particularly proteoglycans. Proteins that are associated with chondrocyte cell mem- branes are also listed because they permit specific interactions with extracellular matrix proteins.