Inhibition of STAT5A promotes osteogenesis by DLX5 regulation

Kyoung Mi Lee; Kwang Hwan Park; Ji Suk Hwang; Moses Lee; Dong Suk Yoon; Hyun Aae Ryu; Ho Sun Jung; Ki Won Park; Jihyun Kim; Sahng Wook Park; Sung Hwan Kim; Yong Min Chun; Woo Jin Choi; Jin Woo Lee

doi:10.1038/s41419-018-1184-7

Inhibition of STAT5A promotes osteogenesis by DLX5 regulation

Kyoung Mi Lee, Kwang Hwan Park, Ji Suk Hwang, Moses Lee, Dong Suk Yoon, Hyun Aae Ryu, Ho Sun Jung, Ki Won Park, Jihyun Kim, Sahng Wook Park, Sung Hwan Kim, Yong Min Chun, Woo Jin Choi, Jin Woo Lee

Department of Orthopaedic Surgery

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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	https://doi.org/10.1038/s41419-018-1184-7
Publication status	Published - 2018 Nov 1

Bibliographical note

Funding 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.

Publisher Copyright:
© 2018, The Author(s).

All Science Journal Classification (ASJC) codes

Immunology
Cellular and Molecular Neuroscience
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41419-018-1184-7

Cite this

@article{ebce4389d7794ab6a405c5e551de9708,

title = "Inhibition of STAT5A promotes osteogenesis by DLX5 regulation",

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.",

author = "Lee, {Kyoung Mi} and Park, {Kwang Hwan} and Hwang, {Ji Suk} and Moses Lee and Yoon, {Dong Suk} and Ryu, {Hyun Aae} and Jung, {Ho Sun} and Park, {Ki Won} and Jihyun Kim and Park, {Sahng Wook} and Kim, {Sung Hwan} and Chun, {Yong Min} and Choi, {Woo Jin} and Lee, {Jin Woo}",

note = "Funding 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. Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = nov,

day = "1",

doi = "10.1038/s41419-018-1184-7",

language = "English",

volume = "9",

journal = "Cell Death and Disease",

issn = "2041-4889",

publisher = "Nature Publishing Group",

number = "11",

}

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, Jin Woo

N1 - Funding 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. Publisher Copyright: © 2018, The Author(s).

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

C2 - 30429452

AN - SCOPUS:85056589372

VL - 9

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 11

M1 - 1136

ER -

Inhibition of STAT5A promotes osteogenesis by DLX5 regulation

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this