TY - JOUR
T1 - PPARγ in bone homeostasis
AU - Wan, Yihong
N1 - Funding Information:
We thank D. Mangelsdorf, S. Kliewer, P. Dechow, J. Zerwekh, and O. Oz (University of Texas Southwestern Medical Center) for helpful discussion, and A. Gray for administrative assistance. We also thank all the investigators whose studies contributed to the understanding of PPARγ actions in bone but could not be cited here because of space limitations. Y. Wan is a Virginia Murchison Linthicum Scholar in Medical Research. This work was supported by the University of Texas Southwestern Medical Center Endowed Scholar Startup Fund, a BD Biosciences Research Grant Award and CPRIT funding (RP100841).
PY - 2010/12
Y1 - 2010/12
N2 - The nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ is a crucial cellular and metabolic switch that regulates many physiologic and disease processes. Emerging evidence reveals that PPARγ is also a key modulator of skeletal remodeling. Long-term use of rosiglitazone, a synthetic PPARγ agonist and a drug to treat insulin resistance, increases fracture rates among patients with diabetes. Recent studies have revealed that PPARγ activation not only suppresses osteoblastogenesis, but also activates osteoclastogenesis, thereby decreasing bone formation while sustaining or increasing bone resorption. The pro-osteoclastogenic effect of rosiglitazone is mediated by a transcriptional network comprised of PPARγ, PPAR-gamma coactivator 1β and estrogen-related receptor α, which promotes both osteoclast differentiation and mitochondrial activation. Therefore, PPARγ plays dual roles in bone homeostasis by regulating both mesenchymal and hematopoietic lineages.
AB - The nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ is a crucial cellular and metabolic switch that regulates many physiologic and disease processes. Emerging evidence reveals that PPARγ is also a key modulator of skeletal remodeling. Long-term use of rosiglitazone, a synthetic PPARγ agonist and a drug to treat insulin resistance, increases fracture rates among patients with diabetes. Recent studies have revealed that PPARγ activation not only suppresses osteoblastogenesis, but also activates osteoclastogenesis, thereby decreasing bone formation while sustaining or increasing bone resorption. The pro-osteoclastogenic effect of rosiglitazone is mediated by a transcriptional network comprised of PPARγ, PPAR-gamma coactivator 1β and estrogen-related receptor α, which promotes both osteoclast differentiation and mitochondrial activation. Therefore, PPARγ plays dual roles in bone homeostasis by regulating both mesenchymal and hematopoietic lineages.
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U2 - 10.1016/j.tem.2010.08.006
DO - 10.1016/j.tem.2010.08.006
M3 - Review article
C2 - 20863714
AN - SCOPUS:78650257620
SN - 1043-2760
VL - 21
SP - 722
EP - 728
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 12
ER -