期刊
STEM CELLS
卷 26, 期 8, 页码 2042-2051出版社
WILEY
DOI: 10.1634/stemcells.2008-0149
关键词
hematopoietic stem cells; niche; osteoblasts; mesenchymal stem cells; endosteal
资金
- NCI NIH HHS [P01 CA093900] Funding Source: Medline
- NIAMS NIH HHS [P30 AR046024] Funding Source: Medline
- NIDCR NIH HHS [R01 DE013701, R56 DE011723, DE13835, R01 DE013835, DE11723, DE13701, R01 DE011723] Funding Source: Medline
- NIDDK NIH HHS [DK53904, R56 DK053904, R01 DK053904] Funding Source: Medline
Crosstalk between hematopoietic stem cells (HSCs) and the cells comprising the niche is critical for maintaining stem cell activities. Yet little evidence supports the concept that HSCs regulate development of the niche. Here, the ability of HSCs to directly regulate endosteal development was examined. Marrow was isolated 48 hours after stressing mice with a single acute bleed or from control nonstressed animals. Stressed and nonstressed HSCs were cocultured with bone marrow stromal cells to map mesenchymal fate. The data suggest that HSCs are able to guide mesenchymal differentiation toward the osteoblastic lineage under basal conditions. HSCs isolated from animals subjected to an acute stress were significantly better at inducing osteoblastic differentiation in vitro and in vivo than those from control animals. Importantly, HSC-derived bone morphogenic protein 2 (BMP-2) and BMP-6 were responsible for these activities. Furthermore, significant differences in the ability of HSCs to generate a BMP response following stress were noted in aged and in osteoporotic animals. Together these data suggest a coupling between HSC functions and bone turnover as in aging and in osteoporosis. For the first time, these results demonstrate that HSCs do not rest passively in their niche. Instead, they directly participate in bone formation and niche activities.
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