OSTEOBLAST-LIKE CELLS FROM HUMAN SUBCHONDRAL OSTEOARTHRITIC BONE DEMONSTRATE AN ALTERED PHENOTYPE IN-VITRO - POSSIBLE ROLE IN SUBCHONDRAL BONE SCLEROSIS

Objective. Osteoarthritis (OA) is accompanied by subchondral bone scle rosis, The present study was undertaken to determine whether osteoblas t-like cells in patients with OA show an abnormal phenotype that could contribute to this sclerosis, Methods, Explants and primary in vitro osteoblast-like cell cultures were prepared from subchondral bone spec imens from OA patients or from bone removed at autopsy from individual s showing no signs of OA or metabolic bone disease. We measured the ab undance and activity of urokinase plasminogen activator (uPA), and the levels of PA inhibitor (PAI-1) and insulin-like growth factor 1 (IGF- 1) in conditioned media from both explants and osteoblast-like cells. The expression of osteoblast phenotypic biomarkers was also evaluated. Results. OA explants showed increased levels and activity of uPA, no changes in PAI-1 abundance, and increases in IGF-1 release, as compare d with preparations from normal individuals. In vitro primary osteobla st-like cells showed results similar to the ex vivo findings for uPA, PAI-1, and IGF-1, Primary OA osteoblast-like cells also expressed high er alkaline phosphatase activity and osteocalcin release than normal c ells, both under basal conditions and with 1,25(OH)(2)D-3 (1,25-dihydr oxyvitamin D) stimulation. Conversely, OA osteoblast-like cells showed blunted cAMP synthesis in response to human parathyroid hormone and p rostaglandin E-2 in contrast to the finding with normal osteoblast-lik e cells, a result that could not be attributed to altered adenylate cy clase activity. Conclusion. Ex vivo and in vitro results indicate simi lar altered activities of OA osteoblasts as compared with normal cells . This suggests that an altered phenotype of subchondral osteoblasts m ay be a contributing factor in human OA.