Consequences of chondrocyte hypertrophy on osteoarthritic cartilage: potential effect on angiogenesis

Abstract

Objective: The aim of this study was to investigate the link between the hypertrophic phenotype of chondrocytes and angiogenesis in osteoarthritis (OA) and more particularly to demonstrate that OA hypertrophic chondrocytes potentially express a phenotype promoting angiogenesis through the expression of factors controlling endothelial cells migration, invasion and adhesion.

Method: Human OA chondrocytes were cultivated in alginate beads in medium supplemented with 10% fetal bovine serum (FBS) to induce chondrocyte hypertrophy. The hypertrophic phenotype was characterized throughout 28 days of culture by measuring the expression of specific genes and by a microscopic observation of cellular morphology. The effect of media conditioned by OA hypertrophic chondrocyte on endothelial cells migration, invasion and adhesion was evaluated in functional assays. Moreover, hypertrophic OA chondrocytes were tested for the expression of angiogenic factors by real-time RT-PCR.

Results: Specific markers of hypertrophy and observation of cellular morphology attested of the hypertrophic phenotype of chondrocytes in our culture model. Functional angiogenesis assays showed that factors produced by hypertrophic chondrocytes stimulated migration, invasion and adhesion of endothelial cells. Among the evaluated angiogenic factors, bone sialoprotein (BSP) was the most highly upregulated in hypertrophic chondrocytes. The inhibition of endothelial cell adhesion by a GRGDS peptide confirmed the implication of RGD domain proteins, like BSP, in hypertrophic chondrocyte-induced adhesion of endothelial cells.

Conclusion: Hypertrophic differentiation of chondrocyte may promote angiogenesis. Our findings established the relation of BSP with OA chondrocyte hypertrophy and suggested that this factor could constitute a potential target to control cartilage neovascularisation in OA.

Keywords: Angiogenesis; Bone sialoprotein; Chondrocyte hypertrophy; Osteoarthritis.