Osx transcriptional regulation is mediated by additional pathways to BMP2/Smad signaling

• Published in: Journal of cellular biochemistry 2005-06, Vol.95 (3), p.518-528
• Main Authors: Celil, Ayse B., Hollinger, Jeffrey O., Campbell, Phil G.
• Format: Article
• Language: English
• Subjects: Animals; BMP-2; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - metabolism; DNA-Binding Proteins - metabolism; Gene Expression Regulation - physiology; human mesenchymal stem cells; Humans; IGF-I; MAPK; Mice; Osx; real-time RT-PCR; Runx2; Signal Transduction - physiology; Smad Proteins; Sp7 Transcription Factor; Stem Cells - physiology; Trans-Activators - metabolism; Transcription Factors - metabolism; Transcription, Genetic - physiology; Transforming Growth Factor beta - metabolism
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.20429

Bone morphogenetic protein (BMP)‐2 induces Osterix (Osx) in mouse C2C12 cells and chondrocytes. Genetic studies place Osx downstream to the BMP‐2/Smad/Runx2 signaling pathway; however, limited information is available on the mediators of Osx expression in osteoblast lineage commitment. Several lines of research implicate the presence of Runx2‐independent ossification. Therefore, the purpose of this study was to identify possible mediators of Osx expression beyond the BMP‐2/Smad pathway. Using real‐time RT‐PCR, we showed upregulation of Osx in response to BMP‐2 in human mesenchymal stem cells (hMSC). Insulin‐like growth factor (IGF)‐I upregulated Osx, but not Runx2. Further, IGF‐I in combination with BMP‐2 was synergistic for Osx, suggesting a pathway beyond Smad signaling. MAPK was tested as a common mediator across BMP‐2 and IGF‐I signaling pathways. Inhibition of MAPK component ERK1/2 did not affect Runx2 gene expression, but inhibited Osx expression and matrix mineralization. BMP‐2‐mediated Osx expression was downregulated in response to p38 inhibition. We therefore conclude that during osteogenic lineage progression, in addition to the BMP‐2/Smad pathway, IGF‐I and MAPK signaling may mediate Osx. © 2005 Wiley‐Liss, Inc.