ERR receptors as potential targets in osteoporosis.
The bone fragility and increased fracture risk associated with osteoporosis in post-menopausal women is a major public health concern. Current treatments for osteoporosis relying on hormone replacement therapies are suspected to have an association with increased breast cancer risk, highlighting the need for identifying new potential targets in bone. Recent data suggest that the estrogen-related receptor (ERR)α, an orphan nuclear receptor, represses osteoblast differentiation, and that its deletion in knockout mouse models results in increased mineral density. Furthermore, modulation of ERRα activity reduces proliferation and tumorigenesis of breast cancer cells. These results indicated that inhibition of ERRα might provide a treatment for osteoporosis without displaying adverse effects in breast cancer. This review focuses on the role of the ERR receptors, and in particular ERRα, in the differentiation of bone precursor cells and its consequences on bone homeostasis, and discusses the possible grounds for the discrepancies reported in the literature.
Gallet
Marlène
M
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon cedex 07, France.
Vanacker
Jean-Marc
JM
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D006801:Humans; D010006:Osteoblasts / Q000166:cytology; D010024:Osteoporosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor