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Newly discovered role for osteocytes in normal myelopoiesis
Fulzele et al. generated osteocyte-specific knockout mice to investigate how Gsα signaling between osteocytes and other cells in the bone microenvironment impacts on hematopoiesis regulation.
The Gsα knockout mice showed a 70% reduction in Gsα expression in osteocytes, but normal expression levels in osteoblasts. The mice developed osteopenia, with reduced cortical and trabecular bone and lowered bone mineral density and bone mineral content. The mice also showed abnormalities in the spleen and bone marrow, and increased levels of leukocytes and platelets in peripheral blood. The authors propose that disruption of Gsα signaling in the mice prevents normal hematopoiesis, leading to an expansion of myeloid cells in hematopoietic organs.
The study revealed that osteocyte-dependent alterations in the bone marrow microenvironment were responsible; these occurred independently of the decrease in osteoblast numbers observed and independently of the apparent suppression of Wnt/β-catenin signaling. The role of Gsα signaling in normal myelopoiesis was confirmed by in vitro studies showing that media from osteocyte-enriched bone explants from the Gsα knockout mice could increase proliferation of myeloid cells, an effect that is partially dependent on osteocyte-derived granulocyte colony-stimulating factor (G-CSF).
Editor’s comment: This study demonstrates a new role for osteocytes. In addition to their role in the regulation of bone remodeling, bone mineralization and phosphate homeostasis, osteocytes are shown here to control myelopoiesis in the bone marrow.
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