Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Gene Expression Profile Associated with the Differentiation of Osteoblasts from Human Mesenchymal Stem Cells

인간 중간엽 줄기세포로부터 골아세포로의 분화시 관찰되는 유전자 발현 분석

  • Kim Yeo-Kyeoung (Department of Hematology/Oncology, Chonnam National University Medical School) ;
  • Kim Hee-Nam (Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital) ;
  • Lee Il-Kwon (Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital) ;
  • Park Kyeong-Soo (Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital) ;
  • Yang Deok-Hwan (Department of Hematology/Oncology, Chonnam National University Medical School) ;
  • Cho Sang-Hee (Department of Hematology/Oncology, Chonnam National University Medical School) ;
  • Lee Je-Jung (Department of Hematology/Oncology, Chonnam National University Medical School) ;
  • Chung Ik-Joo (Department of Hematology/Oncology, Chonnam National University Medical School) ;
  • Kim Soon-Hag (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Kim Hyeoung-Joon (Department of Hematology/Oncology, Chonnam National University Medical School, Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital)
  • 김여경 (전남대학교 의과대학 혈액종양내과) ;
  • 김희남 (전남대학교병원 조혈계질환 유전체 연구센터) ;
  • 이일권 (전남대학교병원 조혈계질환 유전체 연구센터) ;
  • 박경수 (전남대학교병원 조혈계질환 유전체 연구센터) ;
  • 양덕환 (전남대학교 의과대학 혈액종양내과) ;
  • 조상희 (전남대학교 의과대학 혈액종양내과) ;
  • 이제중 (전남대학교 의과대학 혈액종양내과) ;
  • 정익주 (전남대학교 의과대학 혈액종양내과) ;
  • 김순학 (서울대학교 의과대학 핵의학과) ;
  • 김형준 (전남대학교 의과대학 혈액종양내과, 전남대학교병원 조혈계질환 유전체 연구센터)
  • Published : 2006.04.01
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Abstract

Human mesenchymal stem cells (hMSCs) in bone marrow (BM) can be induced to differentiate into a variety of mesenchymal tissues, including adipocytes, osteoblasts and chondroblasts, under the influence of certain growth or environmental factors. In this study, we analyzed the differentiation process and the associated gene expression profiles inherent to the process by which hMSCs differentiate into osteoblasts. We conducted a comparison of gene expression profiles of the normal human BM MSCs, using human 8K cDNA microarray, incubated in media containing either a combination of $\beta$-glycerol phosphate, L-ascorbic acid, and dexamethasone, or in medium lacking these osteogenic supplements. During the osteoblastic differentiation process, 36 genes were determined to be up-regulated, and 59 genes were shown to be down-regulated. Osteoprotegerin, LRP5, and metallothionein 2A, all of which are associated with the osteogenetic process, were up-regulated, and genes associated with the differentiation of MSCs into other lineages, including muscle, adipose tissue and vascular structure were down-regulated. The set of differentially expressed genes reported in this work should contribute to our current understanding of the processes inherent to the differentiation of MSCs into osteoblasts.

인체의 골수내에 존재하는 중간엽 줄기세포는 성장인자나 환경적 요인에 의해 지방세포, 골아세포, 연골모세포 및 연골세포 등으로 분화됨이 알려져 있다. 본 연구에서는 정상 인체의 골수으로 얻어진 중간엽 줄기세포로부터 골아세포의 분화 가능성을 알아보고 이에 관여하는 유전자의 발현을 조사하였다. 정상 골수의 중간엽 줄기세포를 골유도성 자극보조제로서 $\beta$-glycerol phosphate, L-ascorbic acid 및 dexamethasone을 첨가하여 골아세포로의 분화를 유도한 세포와 골유도성 자극보조제를 첨가하지 않은 세포를 배양하여 일정 간격으로 cDNA microarray를 이용하여 각각의 단계에서 발현되는 유전자를 검사하고 이로 인해 얻어진 유전자의 발현량을 분석하기 위해 real time quantitative RT-PCR 을 시행하였다. 골유도성 자극보조제를 첨가한 군에서 첨가하지 않은 군에 비하여 정상적인 골아세포로의 성장이 유도되었고, 분화과정에서 36개의 유전자의 발현이 증가되었고, 59개의 유전자의 발현이 억제되었다. 주로 골 생성 과정과 연관이 있다고 알려진 osteoprotegerin, LRP5 및 metallothionein 2A 등의 유전자들이 분화과정에서 발현 증가되어 나타났고, 줄기세포로부터 분화될 수 있는 조직들 중 근육, 지방, 연골, 혈관 및 신경 조직과 연관된 유전자들은 분화 후기에 감소하거나 혹은 전분화 과정 동안 발현이 억제되었다. 본 연구에서는 골아세포의 분화와 연관된 유전자 발현을 확인함으로써 특정 조건하에서 중간엽 줄기세포로부터 골아세포로의 분화가 가능함을 확인할 수 있었고, 이 과정에 관련된 특정 유전자의 발현 양상을 밝힐 수 있었다.

Keywords

References

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