Resolving the Two “Bony” Faces of PPAR-γ

Author:

Lecka-Czernik Beata,Suva Larry J.

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-γactivity leads to bone loss, similar to the bone loss observed with aging, whereas decreased PPAR-γactivity results in increased bone mass. Emerging evidence suggests that the pro-adipocytic and the anti-osteoblastic properties of PPAR-γare ligand-selective, suggesting the existence of multiple mechanisms by which PPAR-γcontrols bone mass and fat mass in bone.

Funder

National Institute on Aging

Publisher

Hindawi Limited

Subject

Pharmacology (medical),Drug Discovery

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