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

白介素1(IL-1)是一种促炎细胞因子，是骨吸收的有力刺激因子和骨形成的抑制因子。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(ALPase)活性、矿化结节形成和细胞外基质蛋白表达的影响。我们的结果提示，IL-1α通过减少成骨细胞的ALPase和I型胶原的产生来抑制成骨。我们还检测了炎症介质IL-1α对大鼠成骨细胞巨噬细胞集落刺激因子、护骨素和前列腺素E_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通过增加M-CSF和PGE_2的产生，减少成骨细胞的骨保护素的产生，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。这个图尔诺夫…更多的ER受基质金属蛋白酶(MMPs)、基质金属蛋白酶组织抑制物(TIMPs)和纤溶酶原激活系统的调节，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物-1(PAI-1)。结果提示，IL-1α通过增加成骨细胞MMPs、tPA和uPA的产生，减少PAI-1的产生，促进骨基质的转换，并使其向溶解的方向发展。M-CSF和RANKL是破骨细胞分化的必要条件和充分条件。我们以RAW264.7细胞为破骨细胞前体，观察了IL-1α、RANKL和/或M-α对破骨细胞碳酸氢酶II(CA II)、组织蛋白酶K、基质金属蛋白酶-9、RANK、M-CSF受体和c-fos转录因子表达的影响。结果表明，RAW264.7细胞中CAⅡ、组织蛋白酶K和基质金属蛋白酶-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

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