Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis
Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis
- 주제(키워드) Osteoporosis , adipogenesis , Mesenchymal stem cell , Transcriptome
- 발행기관 아주대학교
- 지도교수 정윤석
- 발행년도 2018
- 학위수여년월 2018. 8
- 학위명 박사
- 학과 및 전공 일반대학원 의학과
- 실제URI http://www.dcollection.net/handler/ajou/000000027794
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and adipogenesis. In the present study, I aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries. RNA sequencing (RNA-seq) was carried out using next-generation sequencing (NGS) technology. DEGs were identified using RNA-seq data. Ingenuity pathway analysis (IPA) was used to elucidate the common pathway related to osteoporosis and adipogenesis. Candidate genes for the common pathway were validated with other independent osteoporosis and obese subjects using RT-PCR (reverse transcription-polymerase chain reaction) analysis. Fifty-three DEGs were identified between postmenopausal osteoporosis patients and normal bone mineral density (BMD) controls. Most of the genetic changes were related to the differentiation of cells. The nuclear receptor subfamily 4 group A (NR4A) family was identified as possible common genes related to osteoporosis and adipogenesis. The expression level of the mRNA of NR4A1 was significantly higher in osteoporosis patients than in controls (p=0.018). The expression level of the mRNA of NR4A2 was significantly higher in obese patients than in controls (p=0.041). Some genetic changes in MSCs are involved in the pathophysiology of osteoporosis. The NR4A family might comprise common genes related to osteoporosis and adipogenesis.
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ABSTRACT i
TABLE OF CONTENTS iii
LIST OF FIGURES iv
LIST OF TABLES vi
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 3
Ⅲ. RESULTS 13
Ⅳ. DISCUSSION 30
Ⅴ. CONCLUSION 35
REFERENCES 36
국문요약 42
