The regulation of osteogenesis is important for bone formation and fracture healing. Despite advances in understanding the molecular mechanisms of osteogenesis, crucial modulators in this process are not well-characterized. Here we demonstrate that suppression of signal transducer and activator of transcription 5A (STAT5A) activates distal-less homeobox 5 (DLX5) in human bone marrow-derived stromal cells (hBMSCs) and enhances osteogenesis in vitro and in vivo. We show that STAT5A negatively regulates expression of Dlx5 in vitro and that STAT5A deletion results in increased trabecular and cortical bone mass and bone mineral density in mice. Additionally, STAT5A deletion prevents age-related bone loss. In a murine fracture model, STAT5A deletion was found to significantly enhance bone remodeling by stimulating the formation of a fracture callus. Our findings indicate that STAT5A inhibition enhances bone formation by promoting osteogenesis of BMSCs.
Bibliographical noteFunding Information:
This work was supported by the Mid-career Researcher Program (NRF-2018R1A2B6007376) and by the Basic Science Research Program (NRF-2016R1D1A1B03933182) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education.
© 2018, The Author(s).
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research