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

白介素-1（IL-1）是一种促炎细胞因子，是骨骼分辨率和骨形成抑制剂的潜在刺激剂。我们检查了IL-1α对大鼠骨肉瘤细胞系中细胞增殖，醇磷酸酶（ALPase）活性，矿化淋巴结的形成以及细胞外基质蛋白的表达的影响。我们的结果表明，IL-1α通过通过成骨细胞减少ALPase和I型胶原蛋白产生的降低来抑制成骨。我们还检查了炎症介质IL-1α对巨噬细胞刺激因子（M-CSF），骨蛋白蛋白蛋白蛋白酶（OPG）和Prostaglandin E_2（PGE_2）在大鼠成成成成成成成成成成层中的表达的影响，以及IL-1α对IL-1α对IL-1α造型的效果。我们的结果表明，IL-1α通过增加M-CSF和PGE_2的产生刺激了破骨细胞样细胞的形成，而成骨细胞的OPG产生降低。 IL-1在改变骨基质周转方面起着关键作用。此转弯……更多的ER受基质金属蛋白酶（MMP），基质金属蛋白酶（TIMP）的组织抑制剂（TIMP）和纤溶酶原活化系统的调节，包括组织型纤溶酶原激活剂（TPA），尿毒酶型纤维酶型质激素激活剂（UPA）和质子蛋白激活者（PPE） - 1-1-1-我们的结果表明，IL-1 A通过增加MMP，TPA和UPA产生并通过成骨细胞减少PAI-1的产生来刺激骨基质的周转率，并将周转率倾斜到分辨率。 M-CSF和等级配体（RANKL）是必不可少的，足以足以破骨细胞分化。我们检查了IL-1α或RANKL和/或M-CSF在IL-1α存在下对碳酸酐酶II（CA II），ca蛋白酶K，MMP-9，RANK，M-CSF受体（C-FMS）和C-FOS转录因子的表达的影响，使用RAW264.7细胞作为Osteoclast Pressors。我们的结果表明，在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存在下通过RANKL诱导的。较少的