Multiple extracellular signals promote osteoblast survival and apoptosis
Multiple extracellular signals promote osteoblast survival and apoptosis
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DOI：
10.1210/en.138.9.3849
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发表时间：
1997-09-01
期刊：
影响因子：
4.8
通讯作者：
Meikle, MC
中科院分区：
文献类型：
--
作者：
Hill, PA;Tumber, A;Meikle, MC
细胞凋亡（PCD）是一种在多种细胞类型中诱导的自然发生的细胞自杀途径。在许多情况下，PCD显然是由于竞争有限数量的生存信号而产生的。在这项研究中，我们研究了生长因子（GF），细胞因子，和成骨激素在体外成骨细胞存活的潜在作用。我们的研究结果表明，在这些因素的情况下，成骨细胞迅速经历PCD，由细胞形态，线粒体功能和细胞核碎片。心理状态。胰岛素样生长因子I（IGF-I）、IGF-II、胰岛素和碱性成纤维细胞生长因子（bFGF）促进成骨细胞存活。血小板源性生长因子对成骨细胞的存活没有影响，但这种GF增强了IGF-I、IGF-II和胰岛素的存活促进作用。当bFGF与IGFs或胰岛素联合使用时，也会产生类似的效果。IGF的作用被α IR-3（一种针对I型IGF受体的抗体）阻断，而胰岛素的作用仅被部分阻断。该抗体阻断了血小板衍生生长因子对IGF-I介导的成骨细胞存活的增强作用，但仅部分阻断了bFGF的增强作用。尽管在2%FCS存在下观察到成骨细胞的100%存活，但通过上述GF组合中的任一种获得的最高水平类似于75%。单核细胞衍生因子，肿瘤坏死因子-α（TNF α）是本研究中唯一增强PCD的因子。这些结果表明，成骨细胞的生存促进了骨基质中螯合的GF和I型，而不是II型，IGF受体参与的反应。我们的数据还表明，其他未鉴定的GF或细胞外基质成分可能参与促进成骨细胞存活，TNF α可能在体内消除其作用。我们认为这些生长因子可能在骨吸收阶段从骨基质中释放并促进成骨细胞存活，从而在骨重建中发挥重要作用，并且TNF α诱导的PCD可能有助于炎症性骨病中的骨丢失。
Programed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PCD apparently arises as a result of competition for limiting amounts of survival signals. In this study, we have investigated the potential role of growth factors (GF), cytokines, and osteotropic hormones on osteoblast survival in vitro. Our results indicate that in the absence of any of these factors, osteoblasts rapidly undergo PCD, as determined by cell morphology, mitochondrial function, and nuclei fragmentation. mentation. Osteoblast survival was promoted by insulin-like growth factor I (IGF-I), IGF-II, insulin, and basic fibroblast growth factor (bFGF). Platelet-derived growth factor had no effect an osteoblast survival, but this GF potentiated the survival-promoting effects of IGF-I, IGF-II, and insulin. A similar effect occurred when bFGF was added in combination with either of the IGFs or insulin. The effects of the IGFs were blocked by alpha IR-3, an antibody to the type I IGF receptor, whereas the effects of insulin were only partially blocked. This antibody blocked the potentiating effects of platelet-derived growth factor on IGF-I-mediated osteoblast survival, but only partially blocked those of bFGF. Although a 100% survival of osteoblasts was seen in the presence of 2% FCS, the highest level attained by any of the above GF combinations was similar to 75%. The monocyte-derived factor, tumor necrosis factor-alpha (TNF alpha) was the only agent that enhanced PCD in this study. These results suggest that osteoblast survival is promoted by those GFs sequestrated in bone matrix and that the type I, but not the type II, IGF receptor is involved in the response. Our data also indicate that other unidentified GFs or components of the extracellular matrix may be involved in promoting osteoblast survival and that TNF alpha may abrogate their effects in vivo. We propose that these GFs may be released from bone matrix during phases of bone resorption and promote osteoblast survival, thereby playing an important role in bone remodeling, and that PCD induced by TNF alpha may contribute to the bone loss in inflammatory bone disease.