한빛사논문
- 조회2,361
Abstract
S-H Kook1,2, C-Y Yun2, H-J Sim1, G Bhattarai2, B-C Lee3, K-Y Lee2, E-S Cho2,* and J-C Lee1,2,*
1Department of Bioactive Material Sciences, Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, South Korea
2Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience and School of Dentistry, Chonbuk National University School of Dentistry, Jeonju, South Korea
3University of Pittsburgh Cancer Institute, Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
*Correspondence: Professor E-S Cho or Professor J-C Lee, Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience and School of Dentistry, Chonbuk National University School of Dentistry, Jeonju 561-756, South Korea.
Abstract
Osteoblasts (OBs) are indispensable for the maintenance of hematopoietic stem cells (HSCs) in the bone marrow microenvironment. Here we investigated how Smad4 modulates HSC fate at distinct stages of OB development. For this, we conditionally knocked out Smad4 in cells expressing type I collagen (Col1a1) and osteocalcin (OC), respectively. Col1a1-expressing OBs were widely present in both the trabecular and cortical compartment, whereas OC-expressing OBs were predominantly located in the cortical compartment. HSCs from Col1a1 mutants displayed senescence-associated phenotypes. OC mutants did not exhibit HSC senescence-related phenotypes, but instead showed preferential HSC death. Of note, stromal cell-derived factor 1 expression was lower in Col1a1 mutants than control littermates, suggesting potential impairment of CXCR4-CXCL12-mediated HSC retention. Disruption of the CXCR4-CXCL12 axis by AMD3100 administration led to an increase in the senescence-associated β-galactosidase activity and low competitive potential. Collectively, our findings indicate that deletion of Smad4 in OBs differentially modulates HSC fate in a stage-dependent manner.
논문정보
- Research article
- 2016년 06월 (BRIC 등록일 2016-06-14)
- 국내(교신)+국외 연구진
- 의약학 > 치의학
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