National Center for Cell Science, University of Pune Campus, Pune 411 007, India.
Biochem Biophys Res Commun. 2012 Feb 24;418(4):669-75. doi: 10.1016/j.bbrc.2012.01.074. Epub 2012 Jan 24.
IL-3 is an important cytokine that regulates hematopoiesis. We have previously demonstrated that IL-3 is a potent inhibitor of osteoclastogenesis and bone resorption. In the present study, we have investigated the role of IL-3 on human osteoblast differentiation and bone formation. We found that IL-3 in a dose-dependent manner increases osteoblast differentiation and matrix mineralization in human mesenchymal stem cells (MSCs). IL-3 significantly enhances the expression of osteoblast specific genes such as alkaline phosphatase, collagen type-I, osteocalcin and osteopontin; and Runx-2 and osterix transcription factors. Moreover, IL-3 induces the expression of bone morphogenetic protein-2 (BMP-2), and activates smad1/5/8. IL-3 enhances osteoblast differentiation and BMP-2 secretion through JAK/STAT pathway. Interestingly, IL-3 promotes in vivo bone regeneration ability of MSCs. Thus, we reveal for the first time that IL-3 enhances human osteoblast differentiation and bone formation in both in vitro and in vivo conditions, and suggest its therapeutic potential for bone formation in important bone diseases.
白细胞介素 3（IL-3）是一种重要的细胞因子，调节造血功能。我们之前的研究表明，IL-3 是破骨细胞生成和骨吸收的有效抑制剂。在本研究中，我们研究了 IL-3 对人成骨细胞分化和骨形成的作用。结果发现，IL-3 呈剂量依赖性增加人间充质干细胞（MSCs）中成骨细胞的分化和基质矿化。IL-3 显著增强碱性磷酸酶、I 型胶原、骨钙素和骨桥蛋白等成骨细胞特异性基因以及 Runx-2 和 osterix 转录因子的表达。此外，IL-3 诱导骨形成蛋白-2（BMP-2）的表达，并激活 smad1/5/8。IL-3 通过 JAK/STAT 通路增强成骨细胞分化和 BMP-2 分泌。有趣的是，IL-3 促进 MSCs 的体内骨再生能力。因此，我们首次揭示，IL-3 增强人成骨细胞在体外和体内的分化和骨形成能力，并提示其在重要骨疾病中骨形成的治疗潜力。
