title: Hematopoietic stem cells regulate mesenchymal stromal cell induction into osteoblasts thereby participating in the formation of the stem cell niche.
abstract: 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. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: Department of Periodontics & Oral Medicine, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, Michigan 48109-1078, USA.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Jung
authors.forename: Junhui
authors.initials: J
authors.lastname: Song
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shiozawa
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Wang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Williams
authors.forename: Aaron
authors.initials: A
authors.lastname: Havens
authors.forename: Abraham
authors.initials: A
authors.lastname: Schneider
authors.forename: Chunxi
authors.initials: C
authors.lastname: Ge
authors.forename: Renny T
authors.initials: RT
authors.lastname: Franceschi
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
mesh_terms: D000375:Aging; D000818:Animals; D001846:Bone Development; D001854:Bone Marrow Cells / Q000166:cytology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019070:Cell Lineage; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology*; D010024:Osteoporosis; D013234:Stem Cells / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D019485:Bone Morphogenetic Proteins