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Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 107321, 11 pages
http://dx.doi.org/10.1155/2013/107321
Research Article

NFAT Signaling in Osteoblasts Regulates the Hematopoietic Niche in the Bone Microenvironment

Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA

Received 14 January 2013; Accepted 6 March 2013

Academic Editor: Giacomina Brunetti

Copyright © 2013 Cheryl L. Sesler and Majd Zayzafoon. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Osteoblasts support hematopoietic cell development, including B lymphopoiesis. We have previously shown that the nuclear factor of activated T cells (NFAT) negatively regulates osteoblast differentiation and bone formation. Interestingly, in smooth muscle, NFAT has been shown to regulate the expression of vascular cellular adhesion molecule-1 (VCAM-1), a mediator of cell adhesion and signaling during leukocyte development. To examine whether NFAT signaling in osteoblasts regulates hematopoietic development in vivo, we generated a mouse model expressing dominant-negative NFAT driven by the 2.3 kb fragment of the collagen- I promoter to disrupt NFAT activity in osteoblasts (dnNFATOB). Bone histomorphometry showed that dnNFATOB mice have significant increases in bone volume (44%) and mineral apposition rate (131%) and decreased trabecular thickness (18%). In the bone microenvironment, dnNFATOB mice displayed a significant increase (87%) in LineagecKit+Sca-1+ (LSK) cells and significant decreases in B220+CD19IgM pre-pro-B cells (41%) and B220+CD19+IgM+ immature B cells (40%). Concurrent with these findings, LSK cell differentiation into B220+ cells was inhibited when cocultured on differentiated primary osteoblasts harvested from dnNFATOB mice. Gene expression and protein levels of VCAM-1 in osteoblasts decreased in dnNFATOB mice compared to controls. These data suggest that osteoblast-specific NFAT activity mediates early B lymphopoiesis, possibly by regulating VCAM-1 expression on osteoblasts.