Proliferative response of different human osteoblast-like cell models to proinflammatory cytokines.

Children with inflammatory bowel disease are known to be at risk of osteopenia. The cause of this osteopenia is likely to be multifactorial, but the inflammatory process with its characteristic overproduction of cytokines has been implicated. To investigate this possible contribution of the disease activity to the development of osteopenia, we performed in vitro assays of the proliferation of osteoblast-like cells of differing origins in response to the inflammatory cytokines tumor necrosis factor-alpha and IL-1/beta. Osteoblast-like cells derived from pediatric bone explants, adherent stromal cells derived from bone marrow (osteoprogenitors), MG-63 osteosarcoma cells, and SV-40 virally transformed osteoprogenitor cells (HCC1) were studied. Tumor necrosis factor-alpha stimulated the proliferation of cells in primary cultures (i.e. from explants and marrow samples) in a linear, dose-dependent manner. In contrast, inhibition of proliferation was observed with the established cell lines (MG-63 and HCC1). IL-1beta stimulated proliferation of all cells apart from the immortalized human bone marrow cell line, HCC1, in which case potent inhibition was observed. We conclude that proinflammatory cytokines are potent regulators of osteoblast-like cell proliferation, and that the responses are specific to cell type. The opposite results obtained with established cell lines compared with the primary cultures suggest that careful consideration should be given to choosing the most suitable cell line for in vitro studies relating to in vivo mechanisms predisposing to osteopenia.