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Alteration of Dickkopf-1 and receptor activator of nuclear factor-κB ligand during PBSC mobilization in healthy donors by G-CSF

Bone Marrow Transplantation volume 47, pages 1143–1144 (2012)Cite this article

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The BM microenvironment has a critical role in regulating the proliferation and differentiation of hematopoietic stem cells (HSCs). Recent research has demonstrated that such a microenvironment, the so-called stem cell niche, exists in the osteoblast neighborhood and the blood vessel endothelial cell neighborhood.1 Osteoblasts have been shown to take part in the maintenance and proliferation of HSCs. Further, osteoclasts have a critical role in the mobilization of peripheral HSCs.2 Although the mechanism by which G-CSF mobilizes PBSCs has been extensively studied, it is still not fully understood. Wnt signaling has been shown to have a central role in the development and homeostasis of bone and also has been implicated in the regulation of hematopoiesis.3 To evaluate the biological role of Wnt signaling and osteoclastogenesis in G-CSF-induced PBSC mobilization, we examined serum and plasma levels of Dickkopf-1 (Dkk1), soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin (OPG) in normal healthy donors for allogeneic PBSC transplantation.

The protocol described was approved by our Institutional Review Board. The study participants were 21 healthy donors with a median age of 36 years (range, 14–55 years). After obtaining written informed consent, G-CSF (lenograstim, 10 μg/kg per day or filgrastim, 400 μg/m2 per day) was s.c. administered for 5 days, and apheresis was performed on days 4 and 5. Blood samples from the donors were collected on days 0 and 4, that is, before and during G-CSF-induced PBSC mobilization. On day 4, blood was collected before apheresis to avoid any effects of apheresis on marker levels. After blood collection, serum and plasma from each sample were immediately separated by centrifugation, transferred into cryotubes and stored at −80 °C until further processing. The number of CD34+ cells collected was determined by flow cytometric analysis. Marker levels were measured using ELISAs, according to the manufacturer's protocol. The ELISA kits for Dkk1, sRANKL and OPG were purchased from Biomedica Gruppe (Wien, Austria). Data are presented as mean±s.e.. Differences in marker levels before and during G-CSF treatment were analyzed using the Wilcoxon signed-rank test. P-values of <0.05 were considered significant.

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Authors and Affiliations

  1. Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan

    M Tanaka, T Yujiri, Y Tanaka, N Mitani, A Tanimura & Y Tanizawa

  2. Department of Hematopoietic Stem Cell and Leukemia Research, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan

    T Yujiri & Y Tanaka

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  1. M Tanaka
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Correspondence to T Yujiri.

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Tanaka, M., Yujiri, T., Tanaka, Y. et al. Alteration of Dickkopf-1 and receptor activator of nuclear factor-κB ligand during PBSC mobilization in healthy donors by G-CSF. Bone Marrow Transplant 47, 1143–1144 (2012). https://doi.org/10.1038/bmt.2011.233

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