IL-3 promotes osteoblast differentiation and bone formation in human mesenchymal stem cells

被引:50
作者
Barhanpurkar, Amruta P. [1 ]
Gupta, Navita [1 ]
Srivastava, Rupesh K. [1 ]
Tomar, Geetanjali B. [1 ]
Naik, Sameer P. [1 ]
Joshi, Snehal R. [1 ]
Pote, Satish T. [1 ]
Mishra, Gyan C. [1 ]
Wani, Mohan R. [1 ]
机构
[1] Univ Pune Campus, Natl Ctr Cell Sci, Pune 411007, Maharashtra, India
关键词
IL-3; Mesenchymal stem cells; Osteoblast differentiation; Bone formation; Bone morphogenetic proteins; MORPHOGENETIC PROTEIN-2; OSTEOCLAST DIFFERENTIATION; INFLAMMATORY ARTHRITIS; DOWN-REGULATION; IN-VITRO; ACTIVATOR; INTERLEUKIN-3; EXPRESSION; RESORPTION; FRACTURES;
D O I
10.1016/j.bbrc.2012.01.074
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:669 / 675
页数:7
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