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The effects of zoledronic acid in the bone and vasculature support of hematopoietic stem cell niches
Author(s) -
Soki Fabia.,
Li Xin,
Berry Janice,
Koh Amy,
Sinder Benjamin P.,
Qian Xu,
Kozloff Kenneth M.,
Taichman Russell S.,
McCauley Laurie K.
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24301
Subject(s) - stem cell , bone resorption , microbiology and biotechnology , haematopoiesis , bone marrow , bone remodeling , hematopoietic stem cell , biology , niche , cancer research , medicine , immunology , endocrinology , biochemistry
Hematopoietic stem cells (HSC) are maintained in a tightly regulated bone microenvironment constituted by a rich milieu of cells. Bone cells such as osteoblasts are associated with niche maintenance as regulators of the endosteal microenvironment. Bone remodeling also plays a role in HSC mobilization although it is poorly defined. The effects of zoledronic acid (ZA), a potent bisphosphonate that inhibits bone resorption, were investigated on bone marrow cell populations focusing on HSCs, and the endosteal and vascular niches in bone. ZA treatment significantly increased bone volume and HSCs in both young and adult mice (4 week and 4 month old, respectively). ZA increased vessel numbers with no overall change in vascular volume in bones of young and had no effect on vasculature in adult mice. Since both young and adult mice had increased HSCs and bone mass with differing vasculature responses, this suggests that ZA indirectly supports HSCs via the osteoblastic niche and not the vascular niche. Additionally, gene expression in Lin‐ cells demonstrated increased expression of self‐renewal‐related genes Bmi1 and Ink4a suggesting a role of ZA in the modulation of cell commitment and differentiation toward a long‐term self‐renewing cell. Genes that support the osteoblastic niche, BMP2 and BMP6 were also augmented in ZA treated mice. In conclusion, ZA‐induced HSC expansion occurs independent of the vascular niche via indirect modulation of the osteoblastic niche. J. Cell. Biochem. 114: 67–78, 2012. © 2012 Wiley Periodicals, Inc.