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

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的细胞增殖、碱性磷酸酶（ALP）活性、矿化结节形成和细胞外基质蛋白表达的影响。我们的研究结果表明，IL-1α通过减少成骨细胞产生的ALP和I型胶原来抑制骨生成。本实验还观察了炎症介质IL-1α对大鼠成骨细胞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。结果提示，IL-1α通过促进成骨细胞产生M-CSF和PGE_2，减少OPG，从而促进破骨细胞样细胞的形成。IL-1在改变骨基质转换中起关键作用。这个转弯 ...更多信息 ER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物（tPA）、尿激酶型纤溶酶原激活物（uPA）和纤溶酶原激活物抑制剂1型（派-1））的调节。提示IL-1 α通过增加成骨细胞分泌MMPs、tPA和uPA，减少派-1，促进骨基质转换，使骨基质转换趋向于消退。M-CSF和RANK配体（RANKL）是破骨细胞分化所必需的。我们使用RAW264.7细胞作为破骨细胞前体，检测了IL-1α或RANKL和/或M-CSF在存在IL-1α的情况下对碳酸酐酶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，CA II，组织蛋白酶K，MMP-9在RAW264.7细胞中的表达不是由M-CSF诱导的，而是由RANKL在IL-1α存在下诱导的。少

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