Abstract
Bone loss with aging results from attenuated and unbalanced bone turnover that has been associated with a decreased number of bone forming osteoblasts, an increased number of bone resorbing osteoclasts, and an increased number of adipocytes (fat cells) in the bone marrow. Osteoblasts and adipocytes are derived from marrow mesenchymal stroma/stem cells (MSC). The milieu of intracellular and extracellular signals that controls MSC lineage allocation is diverse. The adipocyte-specific transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) acts as a critical positive regulator of marrow adipocyte formation and as a negative regulator of osteoblast development. In vivo, increased PPAR-γ activity leads to bone loss, similar to the bone loss observed with aging, whereas decreased PPAR-γ activity results in increased bone mass. Emerging evidence suggests that the pro-adipocytic and the anti-osteoblastic properties of PPAR-γ are ligand-selective, suggesting the existence of multiple mechanisms by which PPAR-γ controls bone mass and fat mass in bone.
Highlights
The two-faced ancient Roman god Janus, represents the inseparable relationship between opposites
We summarize the evidence indicating that PPAR-γ is an important regulator of bone homeostasis and marrow mesenchymal stem cell (MSC) differentiation
Aging is associated with changes in the status of MSCs and in the milieu of intrinsic and extrinsic signals that determine the differentiation of MSCs towards osteoblasts and/or adipocytes [1, 10,11,12]
Summary
The two-faced ancient Roman god Janus, represents the inseparable relationship between opposites. In some circumstances, adipocytic and osteoblastic differentiation may occur independently [4, 5], suggesting either an existence in adult marrow of separate pools of progenitor cells responding to proosteoblastic and proadipocytic stimuli differently and/or separate regulatory mechanisms of both osteoblast and adipocyte differentiations. We summarize the evidence indicating that PPAR-γ is an important regulator of bone homeostasis and marrow mesenchymal stem cell (MSC) differentiation. Aging is associated with changes in the status of MSCs and in the milieu of intrinsic and extrinsic signals that determine the differentiation of MSCs towards osteoblasts and/or adipocytes [1, 10,11,12] These changes modulate the continuing dialog between phenotype-specific transcription factors and signals from the microenvironment that collectively determines MSC lineage allocation. The status of MSCs changes with respect to their differentiation
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