Osteogenic differentiation induced by bone morphogenetic proteins can be suppressed by platelet-released supernatant in vitro.

Both bone morphogenetic proteins (BMPs) and growth factors released from activated platelets both occur at sites of bone regeneration but their functional relationship to regulate the temporal and spatial sequence of cellular events is not well defined. Here we investigated whether supernatants derived from activated platelets can modulate the response of the osteogenic cell line MC3T3-E1 to BMPs, and whether BMPs have an effect on MC3T3-E1 cells stimulated with platelet-released supernatant. Platelet-released supernatant suppressed BMP-2-, BMP-6-, and BMP-7-induced osteogenic differentiation of MC3T3-E1 cells, as indicated by the significant decrease in alkaline phosphatase activity and lower levels of osteocalcin transcripts, whereas BMP-2, BMP-6, and BMP-7 did not modulate migration and proliferation of MC3T3-E1 cells, which were stimulated with platelet-released supernatant. Osteogenic differentiation in response to BMPs was not affected after precultivation of MC3T3-E1 cells with platelet-released supernatant. These data suggest that activated platelets can provide a microenvironment that temporarily suppresses the differentiation of osteogenic cells in the presence of BMPs. Future strategies to stimulate bone regeneration should take the suppression of BMP-induced osteogenic differentiation during the existence of the blood clot into account.