Abstract
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.
| Original language | English |
|---|---|
| Article number | 1136 |
| Journal | Cell Death and Disease |
| Volume | 9 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2018 Nov 1 |
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All Science Journal Classification (ASJC) codes
- Immunology
- Cellular and Molecular Neuroscience
- Cell Biology
- Cancer Research
Cite this
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Inhibition of STAT5A promotes osteogenesis by DLX5 regulation. / Lee, Kyoung Mi; Park, Kwang Hwan; Hwang, Ji Suk; Lee, Moses; Yoon, Dong Suk; Ryu, Hyun Aae; Jung, Ho Sun; Park, Ki Won; Kim, Jihyun; Park, Sahng Wook; Kim, Sung Hwan; Chun, Yong Min; Choi, Woo Jin; lee, jinwoo.
In: Cell Death and Disease, Vol. 9, No. 11, 1136, 01.11.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Inhibition of STAT5A promotes osteogenesis by DLX5 regulation
AU - Lee, Kyoung Mi
AU - Park, Kwang Hwan
AU - Hwang, Ji Suk
AU - Lee, Moses
AU - Yoon, Dong Suk
AU - Ryu, Hyun Aae
AU - Jung, Ho Sun
AU - Park, Ki Won
AU - Kim, Jihyun
AU - Park, Sahng Wook
AU - Kim, Sung Hwan
AU - Chun, Yong Min
AU - Choi, Woo Jin
AU - lee, jinwoo
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85056589372&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056589372&partnerID=8YFLogxK
U2 - 10.1038/s41419-018-1184-7
DO - 10.1038/s41419-018-1184-7
M3 - Article
VL - 9
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 11
M1 - 1136
ER -