Kim Hong Sung, Lee Na Kyung
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan 336-745, Korea.
Mol Cells. 2014 Nov;37(11):827-32. doi: 10.14348/molcells.2014.0223. Epub 2014 Nov 5.
The balance between bone formation by osteoblasts and destruction of mineralized bone matrix by osteoclasts is important for bone homeostasis. The increase of osteoclast differentiation by RANKL induces bone diseases such as osteoporosis. Recent studies have shown that insulin is one of main factors mediating the cross-talk between bone remodeling and energy metabolism. However, the systemic examination of insulin-induced differential gene expression profiles in osteoclasts has not been extensively studied. Here, we investigated the global effects of insulin on osteoclast precursors at the level of gene transcription by microarray analysis. The number of genes that were up-regulated by ≥ 1.5 fold after insulin treatment for 6 h, 12 h, or 24 h was 76, 73, and 39; and 96, 83, and 54 genes were down-regulated, respectively. The genes were classified by 20 biological processes or 24 molecular functions and the number of genes involved in 'development processes' and 'cell proliferation and differentiation' was 25 and 18, respectively, including Inhba, Socs, Plk3, Tnfsf4, and Plk1. The microarray results of these genes were verified by real-time RT-PCR analysis. We also compared the effects of insulin and RANKL on the expression of these genes. Most genes had a very similar pattern of expressions in insulin- and RANKL-treated cells. Interestingly, Tnfsf4 and Inhba genes were affected by insulin but not by RANKL. Taken together, these results suggest a potential role for insulin in osteoclast biology, thus contributing to the understanding of the pathogenesis and development of therapeutics for numerous bone and metabolic diseases.
成骨细胞形成骨与破骨细胞破坏矿化骨基质之间的平衡对于骨稳态至关重要。RANKL诱导破骨细胞分化增加会引发骨质疏松等骨疾病。最近的研究表明，胰岛素是介导骨重塑与能量代谢之间相互作用的主要因素之一。然而，胰岛素诱导破骨细胞中差异基因表达谱的系统研究尚未广泛开展。在此，我们通过微阵列分析在基因转录水平上研究了胰岛素对破骨细胞前体的整体影响。胰岛素处理6小时、12小时或24小时后上调≥1.5倍的基因数量分别为76个、73个和39个；下调的基因数量分别为96个、83个和54个。这些基因按20个生物学过程或24个分子功能进行分类，参与“发育过程”和“细胞增殖与分化”的基因数量分别为25个和18个，包括Inhba、Socs、Plk3、Tnfsf4和Plk1。这些基因的微阵列结果通过实时RT-PCR分析进行了验证。我们还比较了胰岛素和RANKL对这些基因表达的影响。大多数基因在胰岛素和RANKL处理的细胞中具有非常相似的表达模式。有趣的是，Tnfsf4和Inhba基因受胰岛素影响，但不受RANKL影响。综上所述，这些结果表明胰岛素在破骨细胞生物学中具有潜在作用，从而有助于理解多种骨和代谢疾病的发病机制及治疗方法的开发。
