The unbearable lightness of bone marrow homeostasis

Abstract

The anatomical and functional dimensions of bone marrow topography have been at the forefront of modern bone and immunological research for many years and remain a source of complexity and perplexity due to the multitude of microhabitats within this microenvironment. In fact, research has uncovered fascinating functional aspects of bone marrow residents, and the bone marrow niche has been identified as the foremost reservoir of a variety of cells including hematopoietic, skeletal and endothelial stem/progenitor cells. The physical interactions of the marrow residents, combined with the release of cytokines and growth factors, organize well-defined operative compartments, which preserve bone and immune cell homeostasis. In a simplistic view, both the hematopoietic and bone marrow stromal (mesenchymal) stem/progenitor cell populations dwell at the interface between the endosteum and the bone marrow area (endosteal niche) and in the perivascular space (vascular niche). Indeed, the tantalizing hypothesis of bone marrow regulatory dependency on these niches is supported by current research insofar as the increase in the number of osteoblasts results in a concomitant increase in the hematopoietic population, indicating that the osteoblasts and the endosteal niche are key components of HSC maintenance. On the other hand, impaired function of the vascular niche compromises the endosteal niche's ability to support hematopoiesis. These fascinating discoveries indicate that there are strong ties between bone marrow inhabitants within the confines of the bone marrow itself. When these ties fail, niche-niche communication suffers and results in reduced bone formation, enfeebled hematopoiesis and unrestrained HSC migration through blood circulation. This study focused on the extraordinary homeostatic equilibrium and function of both bone and immune cells within the spatially defined microenvironment of bone marrow. But how important is the anatomically outlined scenery in which the bone marrow entity supports and hosts the hematopoietic elements?

In vivobiocompatibility of p(HPMAm-lac)-PEG hydrogels hybridized with hyaluronan

“…An integral part of the systemic inflammatory response to toxic compounds is the activation of bone marrow, which results in the release of inflammatory cytokines (Agas et al , ). In the present study, long bones of hydrogel‐ and saline‐treated mice were flushed and the total BMC population was maintained in culture for 3 days.…”

Bone and bone marrow disruption by endocrine‐active substances

“…W. Smith et al, 2013). Hematopoiesis is widely acknowledged as the process by which immature HSCs and progenitor cells differentiate into mature blood and immune cells (Agas et al, 2015;Sabbieti, Marchetti, Censi, Lacava & Agas, 2017). HSC niches within AGAS ET AL.…”

Role of PTH in Bone Marrow Niche and HSC Regulation

“…The wide array of MSC functional and architectural properties provides the required platform for the assembly and organization of the skeletal and perivascular hematopoietic niche framework within the bone marrow. For this reason, MSCs and progenies have been considered for about two decades the preeminent niche manufacturers [2]. In point of fact, it is thought that the different committed MSCs progenies provide signals for HSC differentiation and osteoclastogenesis [6,7], while the in vivo depletion or impaired function of osteoblasts in mice disrupts hematopoiesis.…”

“…Stem, progenitor, and mature hematopoietic cells coordinate bone cell differentiation and matrix deposition. For instance, osteomacs, a specific macrophage subdivision, provide bone-forming signals during the deposition phase [2].…”

“…The physical interactions between the niches, and consequently the fate of the MSCs and HSCs, are broadly influenced by a plethora of autocrine, paracrine, and endocrine Bbone-forming^factors such as bone morphogenetic proteins [23][24][25], growth factors [26], prostaglandins [27][28][29][30][31], shared cytokines and chemokines [2], and hormones such as the parathyroid hormone (PTH) [32]. Although all of these molecules appear to be fundamental for the maintenance of bone microarchitecture and stem/progenitor cell homeostatic features within the bone marrow, PTH has been identified as a key niche element that functionally and spatially links the activities of MSCs and HSCs.…”