Osteoblastic Activation in the Hematopoietic Stem Cell Niche.
From: Endocrine Division, Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA. laura_calvi@urmc.rochester.edu
Annals of the New York Academy of Sciences
- Publish Date: Apr 2006
- ISSN: 0077-8923
- Volume: 1068
- Issue:
- Pages: 477-88
- Medium: Print
- Language: English
- Citation (JAMA): Calvi Laura M, et al. Osteoblastic Activation in the Hematopoietic Stem Cell Niche.. Ann. N. Y. Acad. Sci. Apr 2006;1068:477-88
Abstract
Hematopoietic stem cells (HSC) are rare primitive cells capable of reconstituting all blood cell lineages throughout the life of an individual. The microenvironment in which stem cells reside is essential for their survival, self-renewal, and differentiation. This microenvironment, or HSC niche, has been difficult to define in bone and bone marrow, but recent studies from our laboratory and others have shown that osteoblasts, the bone-forming cells, are an essential regulatory component of this complex cellular network. We established that parathyroid hormone (PTH), through activation of the PTH/PTHrP receptor (PTH1R) in osteoblastic cells, could alter the HSC niche resulting in HSC expansion in vivo and in vitro and improving dramatically the survival of mice receiving bone marrow transplants. These findings are of great clinical appeal, because they suggest that a strategy aimed at modifying supportive cells in a stem cell niche can expand HSC. While a number of molecules have been found to be important for hematopoietic/osteoblastic interactions, we have focused on the Jagged1/Notch signaling pathway, which was necessary for the PTH-dependent HSC expansion. Since the Jagged1/Notch signaling pathway has been implicated in the microenvironmental control of stem cell self-renewal in several organ systems, definition of Jagged1 modulation, which is currently poorly understood, should provide additional molecular targets for stem cell regulation and advance the understanding of stem cell-microenvironmental interactions.
Mesh Headings (Keywords): Animals, Hematopoietic Stem Cells, Humans, Osteoblasts, Parathyroid Hormone, Receptors, Notch, Receptors, Parathyroid Hormone, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 16831945
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.