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Dexras1 plays a pivotal role in maintaining the equilibrium between adipogenesis and osteogenesis

Authors
 Jo Woon Seok  ;  Daeun Kim  ;  Bo Kyung Yoon  ;  Yoseob Lee  ;  Hyeon Ju Kim  ;  Nahee Hwang  ;  Sungsoon Fang  ;  Hyo Jung Kim  ;  Jae-Woo Kim 
Citation
 METABOLISM-CLINICAL AND EXPERIMENTAL, Vol.108 : 154250, 2020-07 
Journal Title
 METABOLISM-CLINICAL AND EXPERIMENTAL 
ISSN
 0026-0495 
Issue Date
2020-07
MeSH
3T3 Cells ; Adipocytes / metabolism ; Adipogenesis / physiology* ; Animals ; Cell Differentiation / physiology ; Cell Line ; Femur / metabolism ; Glucocorticoids / metabolism ; Male ; Mesenchymal Stem Cells / metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteoblasts / metabolism ; Osteoclasts / metabolism ; Osteogenesis / physiology* ; Osteoporosis / metabolism ; RAW 264.7 Cells ; Signal Transduction / physiology ; ras Proteins / metabolism*
Keywords
Adipogenesis ; Cushing's syndrome ; Dexras1 ; Glucocorticoids ; MSCs ; Osteogenesis
Abstract
Background: Chronic steroid treatment causes an increase in visceral adiposity and osteoporosis. It is believed that steroids may alter a balance between differentiation of mesenchymal stem cells (MSCs) into either adipocytes or osteoblasts; however, the detailed molecular mechanisms are unclear. We previously identified Dexras1 as a critical factor that potentiates adipogenesis in response to glucocorticoids. Thus, in this study, we investigated the role of Dexras1 in maintaining the balance between chronic steroid treatment-associated adipogenesis and osteoporosis. Material and methods: We treated wild type (WT) and Dexras1 knockout (KO) mice with dexamethasone for five weeks followed by 60% HFD for additional two weeks with dexamethasone. The changes of glucocorticoid-induced body weight gain and osteoporosis were analyzed. Bone marrow derived stromal cells (BMSCs) and mouse embryonic fibroblasts (MEFs) extracted from WT and Dexras1 KO mice, as well as MC3T3-E1 pre-osteoblasts and osteoclasts differentiated from RAW264.7 were analyzed to further define the role of Dexras1 in osteoblasts and osteoclasts. Results: Dual-energy X-ray absorptiometry and micro-computed tomography analyses in murine femurs revealed that Dexras1 deficiency was associated with increased osteogenesis, concurrent with reduced adipogenesis. Furthermore, Dexras1 deficiency promoted osteogenesis of BMSCs and MEFs in vitro, suggesting that Dexras1 deficiency prevents steroid-induced osteoporosis. We also observed that Dexras1 downregulated SMAD signaling pathways, which reduced the osteogenic differentiation capacity of pre-osteoblast MC3T3-E1 cells into mature osteoblasts. Conclusion: We propose that Dexras1 is critical for maintaining the equilibrium between adipogenesis and osteogenesis upon steroid treatment.
Full Text
https://www.sciencedirect.com/science/article/pii/S0026049520301141
DOI
10.1016/j.metabol.2020.154250
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
3. College of Nursing (간호대학) > Dept. of Nursing (간호학과) > 1. Journal Papers
Yonsei Authors
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Seok, Jo Woon(석조운)
Yoon, Bo Kyung(윤보경)
Fang, Sungsoon(황성순) ORCID logo https://orcid.org/0000-0003-0201-5567
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179587
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