Hematopoietic recovery following chemotherapy is improved by BADGE-induced inhibition of adipogenesis

RJ Zhu, MQ Wu, ZJ Li, Y Zhang, KY Liu - International journal of …, 2013 - Springer
RJ Zhu, MQ Wu, ZJ Li, Y Zhang, KY Liu
International journal of hematology, 2013Springer
This study was designed to investigate the role of increased adipocytes in the bone marrow
(BM) niche induced by high-dose chemotherapy in hematopoietic recovery.
Arabinosylcytosine (Ara-C) was administered to adult C57BL/6J mice to induce
adipogenesis in the BM. We investigated the effects of adipogenesis on hematopoietic
recovery following chemotherapy, using the peroxisome proliferator-activated receptor
gamma inhibitor, bisphenol A diglycidyl ether (BADGE). Adipocyte hyperplasia could be …
Abstract
This study was designed to investigate the role of increased adipocytes in the bone marrow (BM) niche induced by high-dose chemotherapy in hematopoietic recovery. Arabinosylcytosine (Ara-C) was administered to adult C57BL/6J mice to induce adipogenesis in the BM. We investigated the effects of adipogenesis on hematopoietic recovery following chemotherapy, using the peroxisome proliferator-activated receptor gamma inhibitor, bisphenol A diglycidyl ether (BADGE). Adipocyte hyperplasia could be induced by Ara-C treatment in BM and inhibited by BADGE. The accelerated recovery of leukocyte counts, increased colony forming units, and a higher proportion of Ki67+CD45+ BM cells and Ki67+LinSca1+c-kit+ hematopoietic stem cells were observed in the long bone marrow of adipocyte-inhibited mice, as well as an increase in the number of CD45+ BM cells in the tail fatty marrow compared to controls. Adipocytes participated in creating a distinctive niche for hematopoietic cells. In addition, lower expression of stromal cell-derived factor-1α and hypoxia-inducible factor-1 alpha were detected in the BADGE-treated group. These results indicate that hematopoietic recovery is improved following chemotherapy in adipogenesis-inhibited mice. In addition, adipocytes may create an individual niche that affects the proliferation and migration of hematopoietic cells in vitro and in vivo.
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