Mechanism of condensing osteitis crisis following viral infection through toll-like receptors

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The aim of this project is to clarify the mechanisms of condensing osteitis crisis concerning to viral infection. Toll-like receptors (TLR) 1,3-7 expressed in osteoblastic MC3T3-E1 (E1) cells, TLR 1-7 in stromal ST2 cells, and TLR 3,6, and 7 in osteosarcoma cell, MG-63. TLR-3 expression is maximal in all of cells. When these cells were grown to confluent, and then treated with poly I:C for more two weeks, they formed mineralized nodules. It seems to be earlier than in control culture. DNA transfection experiments in with poly I:C treated-MG-63 cells were performed with reporter gene constructs containing 6 copies of cbfa1 or minimal alkaline phosphatase (ALP) promoter fragment. In both cases, the promoter activities increased. Moreover, it was shown using DNA microarray technology that poly I:C increased fibroblast growth factor 2 (FGF 2) mRNA expression in E1 cells. In addition, early growth response 1 (EGR 1), one of the transcription factors of FGF 2, protein expression also increased. Taken together, viral infection in bone tissue might cause to bone mineralization following to activate innate immunity systems of osteoblasts and stromal cells. It was suggested that activation of cbfa 1 following increase of FGF 2 production might be involved in this mechanism. More investigation with signal transduction systems in concerned with activation of FGF 2 signaling might need to elucidate these mechanism in detail.