title: 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.affiliation: National Center for Cell Science, University of Pune Campus, Pune 411 007, India.
authors.forename: Amruta P
authors.initials: AP
authors.lastname: Barhanpurkar
authors.forename: Navita
authors.initials: N
authors.lastname: Gupta
authors.forename: Rupesh K
authors.initials: RK
authors.lastname: Srivastava
authors.forename: Geetanjali B
authors.initials: GB
authors.lastname: Tomar
authors.forename: Sameer P
authors.initials: SP
authors.lastname: Naik
authors.forename: Snehal R
authors.initials: SR
authors.lastname: Joshi
authors.forename: Satish T
authors.initials: ST
authors.lastname: Pote
authors.forename: Gyan C
authors.initials: GC
authors.lastname: Mishra
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Wani
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis; D001861:Bone Regeneration; D002454:Cell Differentiation; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology / Q000502:physiology*; D053650:Interleukin-3 Receptor alpha Subunit / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010006:Osteoblasts / Q000166:cytology*; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis; D053495:Osteopontin / Q000096:biosynthesis; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C115022:IL3RA protein, human; D007377:Interleukin-3; D053650:Interleukin-3 Receptor alpha Subunit; C493709:RUNX2 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase