Chondrocyte phenotyping in human osteoarthritis

Abstract

Cell-ECM (extracellular matrix) interactions are believed to play a key role in maintaining the normal structure of tissues such as cartilage. Cell surface adhesion molecules have been reported to mediate chondrocyte binding to ECM proteins in human normal cartilage but the behaviour of these molecules in human osteoarthritic cartilage is unknown. We studied receptor matrix proteins on freshly isolated chondrocytes obtained from 10 patients with osteoarthritis (OA). Chondrocytes were isolated by enzymatic digestion from three zones of the articular cartilage with a different degree of macroscopic and microscopic damage and chondrocyte phenotype was defined by flow cytometry. Chondrocytes strongly expressed beta1, integrin but not beta3 integrin. LFA-1 (CD18/CD11a) and ICAM-1 (CD54) antigens were almost undetectable. Interestingly, beta1 expression was significantly higher in the minimally damaged zone than in the zones with medium and maximum damage. These data show that beta1-integrin-mediated chondrocyte-ECM interactions decrease in osteoarthritic cartilage suggesting that perturbations of chondrocyte-matrix signalling occurs during OA.

Perturbation of adhesion molecule-mediated chondrocyte-matrix interactions by 4-hydroxynonenal binding: implication in osteoarthritis pathogenesis

“…High ICAM-1 and α1β1 integrin expression levels in the early stages of OA are indicated by several reports in humans and animals [20-22]. In adult joints, increased of β1 integrin was reported in osteoarthritic monkey cartilage compared to normal cartilage [22] and in human OA samples at minimally damaged locations compared to areas with more severe lesions [23]. Knee joints of α1β1-null mice display precocious proteoglycans loss, cartilage erosion associated with increased MMP-2 and MMP-3 expression, and synovial hyperplasia [24,25].…”

The ECM-Cell Interaction of Cartilage Extracellular Matrix on Chondrocytes

“…The α 5 β 1 integrin provides matrix survival signals for normal and osteoarthritic human articular chondrocytes, to prevent apoptosis. Therefore, β -integrin-mediated chondrocyte-ECM interactions are decreased in osteoarthritic cartilage, which suggests that perturbations of chondrocyte-matrix signaling occurs during OA [10, 38, 39]. β 1 integrin, the protein encoded by the ITGB1 gene (also known as CD29 and VLAB) [17], is a multifunctional protein involved in cell-matrix adhesion, cell signaling, cell adhesion, protein binding, and receptor-mediated activity.…”

β1 Integrin Deficiency Results in Multiple Abnormalities of the Knee Joint

“…In the embryonic mouse limb culture system, administration of ␤1 and ␣5 blocking antibodies or RGD peptides induced ectopic joint formation between proliferating and hypertrophic chondrocytes of the growth plate, suggesting that ␣5␤1 integrin controls the decision between cartilage differentiation and joint formation during development (13). In adult joints, increased immunostaining of ␤1 integrin was reported in osteoarthritic monkey cartilage compared with normal cartilage (14) and in human OA samples at minimally damaged locations compared with areas with more severe lesions (15). In another study, the neoexpression of ␣2, ␣4, and ␤2 integrins was observed in osteoarthritic human femoral head cartilage (16).…”