Effects of compression on human subchondral osteoblast metabolism

Abstract

Introduction. Recent data showed that subchondral bone plays an important role in osteoarthritis (OA). Metabolic and morphologic modifications in this tissue contribute to the degradation of the overlaying cartilage. It was suggested that abnormal mechanical pressure exerted onto the articulation was responsible to these changes. Here, we evaluated the effects of compression on osteoblasts from subchondral bone. Method. Osteoblasts were isolated from sclerotic (SC) or non-sclerotic (NSC) areas of human OA subchondral bone. After 28 days, osteoblasts were surrounded by their matrix. This osteoblasts-containing membrane was then placed onto a Biopress Flexercell plate and submitted to a 4h 1.67 MPa compression (1 Hz). Expression of IL-6, IL-8, COX-2, VEGF, IGF-1, OPG and RANKL was evaluated by RT-PCR. IL-6, IL-8 and PGE2 were quantified by ELISA. Results. Basal IL-6, VEGF, COX-2, IGF-1 and RANKL mRNA levels were significantly increased in SC osteoblasts as compared to NSC. By contrast, SC osteoblasts expressed less OPG than those from NSC areas. Compressions induced the expression of genes coding for IL-6, IL-8, COX-2, IGF-1, VEGF and RANKL but decreased the expression of OPG in NSC osteoblasts (p<0.01). Interestingly, compressed NSC osteoblasts expressed similar levels of these genes than SC osteoblasts. Conclusions. We show that our model of compression can induce in NSC osteoblasts a phenotype similar to this observed in sclerotic areas. Moreover, SC osteoblasts are less sensitive to mechanical stimuli than NSC osteoblasts. These results clarify the role of compression in the pathogenesis of subchondral bone sclerosis and allow new perspectives of research in this field