Abstract
Bone marrow stromal cells are critical regulators of hematopoiesis. Osteoblasts are part of the stromal cell support system in bone marrow and may be derived from a common precursor. Several studies suggested that osteoblasts regulate hematopoiesis, yet the entire mechanism is not understood. It is clear, however, that both hematopoietic precursors and osteoblasts interact for the production of osteoclasts and the activation of resorption. We observed that hematopoietic stem cells (HSCs) regulate osteoblastic secretion of various growth factors, and that osteoblasts express some soluble factors exclusively in the presence of HSCs. Osteoblasts and hematopoietic cells are closely associated with each other in the bone marrow, suggesting a reciprocal relationship between them to develop the HSC niche. One critical component regulating the niche is stromal-derived factor-1 (SDF-1) and its receptor CXCR4 which regulates stem cell homing and, as we have recently demonstrated, plays a crucial role in facilitating those tumors which metastasize to bone. Osteoblasts produce abundant amounts of SDF-1 and therefore osteoblasts play an important role in metastasis. These findings are discussed in the context of the role of osteoblasts in marrow function in health and disease.
Highlights
Research supported in part by the Tissue Procurement Core of the University of Michigan Comprehensive Cancer Center, Grant #CA46952, and directly supported by developmental grants from the University of Michigan Core Centers for Musculoskeletal Disorders (AR46024) and awards from the National Institutes of Health (DE13701, PO1-CA-93900)
Bone marrow stromal cells are comprised of different cellular populations including fibroblasts, endothelial and reticular cells, adipocytes and osteoblasts which serve as a rich source of growth factors
Since the formation of the marrow required the coordinated action of osteoblasts and osteoclastic precursors, the absence of osteoblasts producing stromal-derived factor-1 (SDF-1) or hematopoietic cells expressing CXCR4 could limit osteoclastic and subsequent hematopoietic stem cells (HSCs) recruitment into the marrow cavity
Summary
Research supported in part by the Tissue Procurement Core of the University of Michigan Comprehensive Cancer Center, Grant #CA46952, and directly supported by developmental grants from the University of Michigan Core Centers for Musculoskeletal Disorders (AR46024) and awards from the National Institutes of Health (DE13701, PO1-CA-93900). Bone marrow stromal cells are critical regulators of hematopoiesis. We observed that hematopoietic stem cells (HSCs) regulate osteoblastic secretion of various growth factors, and that osteoblasts express some soluble factors exclusively in the presence of HSCs. Osteoblasts and hematopoietic cells are closely associated with each other in the bone marrow, suggesting a reciprocal relationship between them to develop the HSC niche.
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