IL-3 promotes osteoblast differentiation and bone formation in human mesenchymal stem cells
IL-3 promotes osteoblast differentiation and bone formation in human mesenchymal stem cells
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DOI：
10.1016/j.bbrc.2012.01.074
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发表时间：
2012-02-24
影响因子：
3.1
通讯作者：
Wani, Mohan R.
中科院分区：
文献类型：
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作者：
Barhanpurkar, Amruta P.;Gupta, Navita;Wani, Mohan R.
IL-3是调节造血的重要细胞因子。我们先前已经证明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。我们发现IL-3以剂量依赖性方式增加人间充质干细胞（MSC）中的成骨细胞分化和基质矿化。IL-3显著增强成骨细胞特异性基因如碱性磷酸酶、I型胶原蛋白、骨钙蛋白和骨桥蛋白以及Runx-2和osterix转录因子的表达。此外，IL-3诱导骨形态发生蛋白-2（BMP-2）的表达，并激活smad 1/5/8。IL-3通过JAK/STAT途径促进成骨细胞分化和BMP-2分泌。有趣的是，IL-3促进MSC的体内骨再生能力。因此，我们首次揭示了IL-3在体外和体内条件下增强人成骨细胞分化和骨形成，并表明其在重要骨疾病中骨形成的治疗潜力。(C)2012 Elsevier Inc. All rights reserved.
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. (C) 2012 Elsevier Inc. All rights reserved.