Osteoblast Lineage Support of Hematopoiesis in Health and Disease

Abstract

In mammals, hematopoiesis migrates to the bone marrow during embryogenesis coincident with the appearance of mineralized bone, where hematopoietic stem cells (HSCs) and their progeny are maintained by the surrounding microenvironment or niche, and sustain the entirety of the hematopoietic system. Genetic manipulation of niche factors and advances in cell lineage tracing techniques have implicated cells of both hematopoietic and nonhematopoietic origin as important regulators of hematopoiesis in health and disease. Among them, cells of the osteoblast lineage, from stromal skeletal stem cells to matrix-embedded osteocytes, are vital niche residents with varying capacities for hematopoietic support depending on stage of differentiation. Here, we review populations of osteoblasts at differing stages of differentiation and summarize the current understanding of the role of the osteoblast lineage in supporting hematopoiesis. © 2022 American Society for Bone and Mineral Research (ASBMR).

Keywords: BONE MARROW MICROENVIRONMENT; BONE MARROW STROMAL CELLS; HEMATOPOIESIS; HEMATOPOIETIC NICHE; OSTEOBLASTS.

Figure 1.

Developmental progression of hematopoiesis in humans. In mammals, the yolk sac is the site of the initial wave of hematopoiesis, followed by the aorta-gonad mesonephros (AGM) region of the mesoderm, placenta, and fetal liver. By birth, hematopoiesis shifts to the bone marrow of the axial skeleton, tibias, and femurs. In adulthood, following conversion of red hematopoietically active marrow to yellow, inactive marrow within long bones, the vertebrae, pelvis, sternum, and ribs are the major sites of hematopoiesis. (Adapted from Papayannopoulou T, Migliaccio AR. Chapter 26 - Biology of Erythropoiesis, Erythroid Differentiation, and Maturation. In: Ronald H, Edward JB, Leslie ES, Helen EH, Jeffrey IW, John A, et al., editors. Hematology (Seventh Edition). Seventh Edition ed: Elsevier; 2018. p. 297–320.e14.)⁽⁷⁾ AGM, aorta-gonad-mesonephros.

Figure 2.

Interactions between osteoblast lineage and hematopoietic cells in the bone marrow. CXCL12, CXC chemokine ligand 12; SCF, stem cell factor; PTN, pleiotrophin; IL-7, interleukin 7; IGF-1, insulin-like growth factor 1; EPO, erythropoietin; DLL4, delta-like ligand 4; OPN, osteopontin; THPO, thrombopoietin, ANGPT1, angiopoietin; G-CSF, granulocyte colony stimulating factor; LepR, leptin receptor; HSC, hematopoietic stem cell; CLP, common lymphoid progenitor; CAR cell, CXCL12-abundant reticular cell.