The effects of zoledronic acid in the bone and vasculature support of hematopoietic stem cell niches

Fabiana N. Soki, Xin Li, Janice Berry, Amy Koh, Benjamin P. Sinder, Xu Qian, Kenneth M. Kozloff, Russell S. Taichman, Laurie K. McCauley

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)67-78
Number of pages12
JournalJournal of Cellular Biochemistry
Volume114
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • BISPHOSPHONATE
  • BLOOD VESSELS
  • BONE VASCULATURE
  • HEMATOPOIETIC STEM CELLS
  • NICHE
  • ZOLEDRONIC ACID

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The effects of zoledronic acid in the bone and vasculature support of hematopoietic stem cell niches'. Together they form a unique fingerprint.

Cite this