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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1173-1181.
Prepublished online as a Blood First Edition Paper on October 30, 2007; DOI 10.1182/blood-2007-03-082800.
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Submitted March 29, 2007
Accepted October 27, 2007
Strontium can increase some osteoblasts without increasing haematopoietic stem cells
Stefania Lymperi, Nicole Horwood, Stephen Marley, Myrtle Y Gordon, Andrew P Cope, and Francesco Dazzi*
Stem Cell Biology Section-Kennedy Institute of Rheumatology, and Division of Investigative Sciences, Imperial College, London, United Kingdom
Department of Haematology, Hammersmith Hospital, Imperial College London, London, United Kingdom
* Corresponding author; email: f.dazzi{at}imperial.ac.uk.
Osteoblasts are a key component in the regulation of the hematopoietic stem cell (HSC) niche. Manipulating osteoblast numbers results in a parallel change in HSC numbers. We tested the activity of strontium (Sr), a bone anabolic agent which enhances osteoblast function and inhibits osteoclast activity, on hematopoiesis. In vitro treatment of primary murine osteoblasts with Sr increased their ability to form bone nodules, whilst in vivo it increased osteoblast number, bone volume, trabecular thickness and decreased trabecular pattern factor. However, the administration of Sr had no influence on primitive HSC, although the number of hematopoietic progenitors was higher than in controls. When Sr-treated mice were used as donors for HSC transplantation no difference in the engraftment ability was observed, whilst hematopoietic recovery was delayed when they were used as recipients. Despite the changes in osteoblast numbers, no increment in the number of N-cadherin+ osteoblasts and N-cadherin transcripts could be detected in Sr-treated mice. Therefore, increasing the overall number and function of osteoblasts without increasing N-cadherin+ cells is not sufficient to enhance HSC quantity and function. Our study further supports the notion that N-cadherin+ osteoblasts are fundamental in the hematopoietic niche.
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