Clarification of molecular mechanism of the extension of dental radicular cysts with osteoclast formation after inflammatory cytokine is stimulated

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Interleukin-1 (IL-1) is a proinflammatory cytokine that is a potent stimulator of bone resorption and an inhibitor of bone formation. We examined the effect of IL-1α on cell proliferation, alkaline phosphatase (ALPase) activity, mineralized nodule formation, and the expression of extracellular matrix proteins in rat osteosarcoma cell lines. Our results suggested that IL-1α suppresses osteogenesis through a decrease in ALPase and type I collagen production by osteoblasts. We also examined the effect of the inflammatory mediator IL-1α on the expression of macrophage colony-stimulating factor (M-CSF), osteoprotegerin (OPG), and prostaglandin E_2 (PGE_2) in rat osteoblasts, and the indirect effect of IL-1α on the formation of osteoclast-like cells. Our results suggested that IL-1α stimulated the formation of osteoclast-like cells via an increase in M-CSF and PGE_2 production, and a decrease in OPG production by osteoblasts. IL-1 plays key roles in altering bone matrix turnover. This turnov … More er is regulated by matrix metalloproteinases (MMPs), tissue inhibitor of matrix metalloproteinases (TIMPs), and the plasminogen activation system, including tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1). Our results suggested that IL-1 a stimulate bone matrix turnover by increasing MMPs, tPA, and uPA production and decreasing PAI-1 production by osteoblasts, and incline the turnover to the resolution. M-CSF and RANK ligand (RANKL) are essential and sufficient for osteoclast differentiation. We examined the effects of IL-1α or RANKL and/or M-CSF in the presence of IL-1α on the expression of carbonic anhydrase II (CA II), cathepsin K, MMP-9,RANK, M-CSF receptor (c-fms), and c-fos transcription factor using RAW264.7 cells as osteoclast precursors. Our results indicated that the expression of CA II, cathepsin K, and MMP-9 in RAW264.7 cells is not induced by M-CSF, but by RANKL in the presence of IL-1α. Less