Skeletogenesis and the Hematopoietic Niche

Abstract

The reciprocal regulation of the skeletal and the immune systems has been clinically appreciated for years. In particular, factors produced by immune cells during homeostasis and activation markedly affect the skeleton, which in turn affects the marrow niche environments (as reviewed in (Compston 2002). This relationship also extends to an interdependence between bone and hematopoiesis during immune cell development, however the critical cell types and extracellular matrix components involved in establishing and maintaining hematopoietic niches within the bone marrow are only recently beginning to be defined. Indeed, some immuno-osseous disorders with hematopoietic defects such as bone marrow failure and immune dysfunction, as well as certain cancers, may result from a defective hematopoietic niche (Spranger et al. 1991; Kuijpers et al. 2004; Hermanns et al. 2005; Walkley et al. 2007; Walkley et al. 2007; Raaijmakers et al. 2010). Likewise during aging, a progressive decline in cell replacement and repair manifests in both the skeletal and hematopoietic systems with reduced bone mass and diminished blood cell formation respectively (as reviewed in (Rossi et al. 2008) and (Gruver et al. 2007). Further, this altered hematopoiesis due to aging leads to deficient immune function and increased incidence of malignancies (Rossi et al. 2005; Janzen et al. 2006; Mayack et al. 2010). Thus, the dynamic relationship between skeletal and hematopoietic maintenance throughout life suggests that these clinical outcomes may ensue from cell signaling deficiencies or from defects in the structural environment supporting hematopoiesis. This chapter provides an overview of our current understanding of how hematopoietic niches may be established, how they promote hematopoiesis, and how the skeletal status may modulate niche function.