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Review
. 2009;19(2):109-24.
doi: 10.1615/critreveukargeneexpr.v19.i2.20.

Marrow fat and the bone microenvironment: developmental, functional, and pathological implications

Clifford J Rosen  1 , Cheryl Ackert-Bicknell, Juan Pablo Rodriguez, Ana Maria Pino
Affiliations
Review

Marrow fat and the bone microenvironment: developmental, functional, and pathological implications

Clifford J Rosen et al. Crit Rev Eukaryot Gene Expr. 2009.

Abstract

Bone marrow adipogenesis is a normal physiologic process in all mammals. However, its function is unknown. The mesenchymal stem cell is the marrow precursor for adipocytes as well as osteoblasts, and PPARG is an essential differentiation factor for entrance into the fat lineage. Mouse models have provided significant insight into the molecular cues that define stromal cell fate. In humans, accelerated marrow adipogenesis has been associated with aging and several chronic conditions, including diabetes mellitus and osteoporosis. Newer imaging techniques have been used to determine the developmental time course of fat generation in bone marrow. However, more studies are needed to understand the interrelationship among hematopoietic, osteoblastic, and adipogenic cells within the marrow niche.

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Figures

FIGURE 1
FIGURE 1
Bone turnover is a coupled process that involves differentiation of precursor cells from the mesenchymal and hematopoietic lineages. Adipocytes and osteoblasts arise from a common mesenchymal cell, or marrow stromal cell, that is multipotent and can differentiate into chondrocytes or muscle cells. The differentiation of adipocytes requires activation by several transcription factors, including Cebpβ and PPARG2. Co-activators and co-repressors are recruited to the transcription complex with activation of PPARG2 and ultimately determine the type and function of the adipocyte. In some instances, activation of adipogenesis can occur at the expense of osteoblast differentiation, which requires a distinct series of transcription factors (Dlx, Runx2, Msx, Osterix). However, lineage allocation may not be mutually exclusive. Activation of PPARG2 also results in recruitment of hematpoietic cells that can differentiate into osteoclasts under the influence of m-CSF and RANKL, which are produced by preosteoblasts, thereby ensuring a coupled process.
FIGURE 2
FIGURE 2
Marrow fat in two inbred strains, C3H/HeJ and C57BL/6J.
See this image and copyright information in PMC

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