Myelopoiesis is regulated by osteocytes through Gsα-dependent signaling

Abstract

Key Points• Deletion of Gs␣ in osteocytes induces severe osteopenia and a dramatic expansion of cells of the myeloid lineage.• Osteocytes regulate hematopoiesis and specifically contribute to myelopoiesis by secreting proliferative factors such as G-CSF.

Regulation of hematopoiesis in endosteal microenvironments

“…Fulzele et al found that osteocytes participate in the regulation of myelopoiesis through the secretion of hematopoietic cytokines, such as G-CSF. They showed that the deletion of Gsa specifically in osteocytes greatly enhances G-CSF production, leading to the expansion of myeloid-committed cells, but not HSCs, in the BM [12].…”

“…A number of important roles for osteocytes in bone biology, such as mechanosensation and mineral metabolism, have been identified in previous studies [11]. A series of recent studies, including one by our group, has revealed the importance of osteocytes in the regulation of hematopoiesis [12][13][14]. In this review, we provide an overview of advances in our knowledge of regulatory mechanisms in the hematopoietic system by osteolineage cells in the endosteal area.…”

The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro

“…Ocy454 cells show rapid, high level expression of SOST/sclerostin that is responsive to hormonal (PTH), cytokine (PGE 2 ), and mechanical stimuli. Furthermore, G s ␣ knockdown in Ocy454 led to significant increases in SOST expression matching known osteocyte in vivo regulation (35), demonstrating the broad utility of this new osteocytic cell line for studying SOST/sclerostin regulation as we have recently reported (36). Ocy454 also showed an enhanced osteocytic phenotype when cultured on a three-dimensional biomaterial by increasing FGF23 expression upon PTH stimulation, highlighting the importance of optimizing in vitro culture conditions for studying certain aspects of osteocyte biology.…”

Neoplasms in the bone marrow niches: disturbance of the microecosystem

“…Several studies found that deletion or mutation of functional genes in these niche cells led to MPNs, myelodysplasia, or leukemia [12,[28][29][30][31][32]. These findings and accordingly raised concepts were proved by the clinical transplantation investigations, in which donor-derived hematologic malignancies after hematopoietic stem cell transplantation were diagnosed [33].…”