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

阐明炎症细胞因子刺激后牙根囊肿扩展伴破骨细胞形成的分子机制

基本信息

批准号：
16591896
负责人：
MAENO Masao
金额：
$ 2.11万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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

白细胞介素-1 (IL-1) 是一种促炎细胞因子，是骨吸收的有效刺激剂和骨形成的抑制剂。我们检测了 IL-1α 对大鼠骨肉瘤细胞系中细胞增殖、碱性磷酸酶 (ALPase) 活性、矿化结节形成和细胞外基质蛋白表达的影响。我们的结果表明，IL-1α 通过减少成骨细胞 ALP 酶和 I 型胶原蛋白的产生来抑制成骨。我们还检测了炎症介质IL-1α对大鼠成骨细胞中巨噬细胞集落刺激因子（M-CSF）、骨保护素（OPG）和前列腺素E_2（PGE_2）表达的影响，以及IL-1α对破骨细胞样细胞形成的间接影响。我们的结果表明，IL-1α 通过增加 M-CSF 和 PGE_2 的产生以及减少成骨细胞的 OPG 产生来刺激破骨细胞样细胞的形成。 IL-1 在改变骨基质周转方面发挥着关键作用。这种转变受基质金属蛋白酶 (MMP)、基质金属蛋白酶组织抑制剂 (TIMP) 和纤溶酶原激活系统（包括组织型纤溶酶原激活剂 (tPA)、尿激酶型纤溶酶原激活剂 (uPA) 和纤溶酶原激活剂抑制剂 1 型 (PAI-1)）的调节。我们的结果表明，IL-1a 通过增加 MMP、tPA 和 uPA 的产生并减少成骨细胞的 PAI-1 的产生来刺激骨基质周转，并使周转倾向于分辨率。 M-CSF 和 RANK 配体 (RANKL) 对于破骨细胞分化至关重要且足够。我们使用 RAW264.7 细胞作为破骨细胞前体，检查了 IL-1α 存在时 IL-1α 或 RANKL 和/或 M-CSF 对碳酸酐酶 II (CA II)、组织蛋白酶 K、MMP-9、RANK、M-CSF 受体 (c-fms) 和 c-fos 转录因子表达的影响。我们的结果表明，RAW264.7 细胞中 CA II、组织蛋白酶 K 和 MMP-9 的表达不是由 M-CSF 诱导的，而是在 IL-1α 存在的情况下由 RANKL 诱导的。较少的