PPARγ , an Essential Regulator of Bone Mass: Metabolic and Molecular Cues

Nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor essential for adipocyte differentiation, insulin signaling, and processes of energy turnover in adipose, liver and muscle tissue. PPARγ also controls bone turnover and regulates bone cell differentiation of both mesenchymal and hematopoietic lineages. Recent evidence suggests that bone is an organ integral to energy metabolism not only with respect to energy storage, but also as an organ regulating systemic energy homeostasis. Since PPARγ is positioned at the crossroads of the control of bone mass and energy metabolism, therapeutic manipulation of its activity may affect bone. Indeed, anti-diabetic thiazolidinedione (TZD) therapy, which targets PPARγ activity, is associated with both decreased bone mass and increased fracture risk. However, the anti-osteoblastic activity of PPARγ can be separated from its metabolic activity by using selective PPARγ agonists, which raises the possibility of the development of therapies beneficial for diabetes and safe for bone. This Perspective reviews current evidence for the role of PPARγ in bone metabolism and bone cell differentiation. It also discusses the role of bone fat in the modulation of the bone marrow microenvironment and a possible contribution of this fat compartment to the systemic regulation of energy metabolism. IBMS BoneKEy. 2010 May;7(5):171-181. 2010 International Bone & Mineral Society