| Budget Amount *help |
¥3,760,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
The precise mechanisms of the growth of keratocystic odontogenic tumor have not been well understood. Bone resorption is essential for the growth in the mandibule. Namely, production of proteolytic enzymes, osteoclastogenesis, and activation of osteoclasts are needed for the bone resorption. It has been suggested that these production and activation are regulated by cytokines. We have shown interleukin-1α (IL-1α), one of inflammatory cytokines, is strongly expressed in the tumors. The pathophysiological function of IL-lα is controlled not only by IL-la itself but also its specific receptor (IL-1R) and its receptor antagonist (IL-1Ra). Thus, we first investigated the expression of IL-1α, IL-1R, and IL-1Ra in the tissue sections, immunohistochemically. The epithelial cells and the fibroblasts in the subepithelial layer expressed IL-1R and IL-1Ra, but the expression of IL-1R decreased after the marsupialization of the tumors. These suggest that pathophysiological function of IL-lα might be decrease after marsupialization in the tumors. The epithelial cells of keratocystic odontogenic tumors show high proliferating activity. We showed in this study that the proliferating activity was regulated by IL-1α-dependent keratinocyte growth factor. Furthermore, we clarified that IL-lα increased cyclooxygenase (COX)-2 expression in the subepithelial layer fibroblasts, increased the expression of prostaglandin E2 (PGE2) , and the enhanced PGE2 indirectly increased the expression of macrophage colony-stimulating factor (M-CSF) and nuclear factor kB ligand (RANKL). In addition, we revealed that the subepithelial layer fibroblasts expressed calcium sensitive receptor (CasR) in the plasma membrane, and the increase of extracellular calcium concentration stimulated the receptor and increased the expression of COX-2 and the secretion of PGE2. Therefore, these findings suggest that IL- 1α may play a crucial role in the bone destruction by the tumors.
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