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. 2014 Dec 10;3(4):263-72.
doi: 10.4161/adip.32215. eCollection 2014 Oct-Dec.

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Meghan A Piccinin  1 , Zia A Khan  2
Affiliations

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Meghan A Piccinin et al. Adipocyte. .

Abstract

Diabetes leads to complications in select organ systems primarily by disrupting the vasculature of the target organs. These complications include both micro- (cardiomyopathy, retinopathy, nephropathy, and neuropathy) and macro-(atherosclerosis) angiopathies. Bone marrow angiopathy is also evident in both experimental models of the disease as well as in human diabetes. In addition to vascular disruption, bone loss and increased marrow adiposity have become hallmarks of the diabetic bone phenotype. Emerging evidence now implicates enhanced marrow adipogenesis and changes to cellular makeup of the marrow in a novel mechanistic link between various secondary complications of diabetes. In this review, we explore the mechanisms of enhanced marrow adipogenesis in diabetes and the link between changes to marrow cellular composition, and disruption and depletion of reparative stem cells.

Keywords: adipogenesis; angiogenesis; diabetes; osteoblasts; repair; stem cells.

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Figures

Figure 1.
Figure 1.
Schematic illustrating bone marrow niche components. Bone marrow contains at least two different stem cell types: hematopoietic stem cells and mesenchymal stem cells. Self-renewal and differentiation activity of these stem cells is regulated by the surrounding microenvironment including cell types at various differentiation states. These niche cells include endothelial cells, osteoblasts, adipocytes and mesenchymal progenitor cells (cells restricted to the mesenchymal lineage). HSC, hematopoietic stem cells; MAPC, multipotential adult progenitor cell; MSC, mesenchymal/multipotential stem cell; SC, stem cell.
Figure 2.
Figure 2.
Effect of diabetes in target organs systems. Diabetes leads to structural and functional changes in target organs resulting in loss of blood vessel integrity and vasoregulation. Continued damage to blood vessels leads to a reduction in blood flow to target organs and loss of vascular cells. Vessel degeneration and ischemia play critical roles in the development of secondary complications of diabetes including retinopathy, nephropathy, and cardiomyopathy. In the bone marrow, diabetes changes the cellular composition by increasing adipogenesis and reducing osteoblastogenesis. These are believed to alter the stem cell niche resulting in stem cell dysfunction and depletion. The end result would be impaired repair and regeneration of vasculature in target organs of secondary complications.
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