Type x collagen synthesis in human osteoarthritic cartilage. indication of chondrocyte hypertrophy

Abstract

Objective. To investigate the appearance of hypertrophic chondrocytes in osteoarthritic (OAj cartilage, using type X collagen as a specific marker.Methods. The biosynthesis of type X collagen was examined by metabolic labeling of freshly isolated articular chondrocytes with 3H-proline, immunoprecipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the synthesized collagens. Extracellular deposition of types X and I1 collagen was analyzed immunohistochemically . Chondrocytes of normal adult articular cartilage are phenotypically similar to fetal chondrocytes of the resting zone, in that they synthesize the same pattern of collagens: types 11, IX, XI, and VI ( 1 4 ) . There are conflicting reports concerning the modulation of the chondrocyte phenotype and associated alterations of collagen synthesis during osteoarthritic (OA) degeneration of articular cartilage. In early stages of human and experimentally induced OA, articular chondrocytes respond to the degenerative events by increasing the synthesis of proteoglycan and type I1 collagen several times higher than normal (5,6); this suggests stability of the chondrocyte phenotype. Other investigators have observed that chondrocytes in the upper zone of OA cartilage stain pericellularly with antibodies to types 1 and I11 collagen (7). Biochemical analyses of articular cartilage, however, have clearly shown that more than 95% of the collagen in both normal and OA cartilage is type I1 collagen, while significant amounts of type I collagen are found only in fibrocartilage (3,8). ResultsThe frequent occurrence of clusters of proliferating, hypertrophic chondrocytes in OA cartilage (9) prompted us to search for type X collagen during various stages of osteoarthritic degeneration of cartilage. Type X collagen is a short, non-fibril-forming collagen which has thus far been found only in hyper-

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

“…It has also been 416 STOKES ET AL shown that chondrocytes within the deep zones of OA cartilage can express type X collagen, indicating that they may be undergoing hypertrophy (8,9,72,73). Others have observed the synthesis by OA chondrocytes of aggrecan molecules that resemble the structure of aggrecan molecules in fetal chondrocytes (11).…”

“…These changes in the biosynthetic profile of dedifferentiated chondrocytes resemble some of the phenotypic changes displayed by OA chondrocytes, and the matrix they produce is similar to that synthesized by chondroprogenitor cells (7)(8)(9)(10)(11)(12)(13)17,(37)(38)(39)(40). However, the mechanisms responsible for the phenotypic instability of chondrocytes and the regulation of these different chondrocyte-specific phenotypes remain poorly understood.…”

“…The chondro-cyte response may lead, in certain situations, to longterm changes in the phenotype of the cell, and therefore to an inability to properly repair or maintain the cartilage ECM (4). This is exemplified by the phenotypic changes in the patterns of production or in the temporal or spatial distribution of the synthesis of interstitial collagens, fibroblast-type proteoglycans, and production of ECM proteins associated with fetal development that occur during the development of osteoarthritis (OA), dedifferentiation in culture, or in response to certain types of cartilage injury (6)(7)(8)(9)(10)(11)(12)(13).…”

Genomic organization and full‐length cDNA sequence of human collagen X

“…It is expressed by hypertrophic chondrocytes in the calcifying zone of the growth plate [1,6], in zones of secondary ossification [ 11, in newly forming osteophytic or reparative cartilage [7,8], or in bone callus during fracture healing [9]. This restricted expression to zones of degrading cartilage implies that collagen type X may play an important role in the regulation of endochondral ossification and cartilage degradation.…”

“…We have recently published studies on the developmental expression in fetal cartilage, in adult h&thy, as well as in osteoarthritic and rheumatoid adult cartilage [1, 7,8] indicating precisely regulated gene activation. Changes of in vitro expression patterns of type X collagen due to the influences of retinoic acid [24], of vitamin D [25] and of calcium j?-glycerophosphate [26] also suggest a precise and highly complex ,regulation of the expression of its gene.…”