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

Abstract

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.

• Authors: Amruta P Barhanpurkar, Navita Gupta, Rupesh K Srivastava, Geetanjali B Tomar, Sameer P Naik, Snehal R Joshi, Satish T Pote, Gyan C Mishra, Mohan R Wani
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 418 Issue 4 Pg. 669-75 (Feb 24 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22293197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• BMP2 protein, human
• Bone Morphogenetic Protein 2
• Collagen Type I
• Core Binding Factor Alpha 1 Subunit
• IL3RA protein, human
• Interleukin-3
• Interleukin-3 Receptor alpha Subunit
• RUNX2 protein, human
• Sp7 Transcription Factor
• SP7 protein, human
• Transcription Factors
• Osteocalcin
• Osteopontin
• Alkaline Phosphatase

Topics

• Alkaline Phosphatase (biosynthesis)
• Animals
• Bone Morphogenetic Protein 2 (biosynthesis)
• Bone Regeneration
• Cell Differentiation
• Collagen Type I (biosynthesis)
• Core Binding Factor Alpha 1 Subunit (biosynthesis)
• Humans
• Interleukin-3 (pharmacology, physiology)
• Interleukin-3 Receptor alpha Subunit (biosynthesis)
• Mesenchymal Stem Cells (cytology, drug effects, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Osteoblasts (cytology)
• Osteocalcin (biosynthesis)
• Osteogenesis
• Osteopontin (biosynthesis)
• Sp7 Transcription Factor
• Transcription Factors (biosynthesis)