PPARβ/δ governs Wnt signaling and bone turnover.

Détails

ID Serval
serval:BIB_77E3BA74B733
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
PPARβ/δ governs Wnt signaling and bone turnover.
Périodique
Nature Medicine
Auteur(s)
Scholtysek C., Katzenbeisser J., Fu H., Uderhardt S., Ipseiz N., Stoll C., Zaiss M.M., Stock M., Donhauser L., Böhm C., Kleyer A., Hess A., Engelke K., David J.P., Djouad F., Tuckermann J.P., Desvergne B., Schett G., Krönke G.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Statut éditorial
Publié
Date de publication
2013
Volume
19
Numéro
5
Pages
608-613
Langue
anglais
Résumé
Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis. Furthermore, PPARγ has been implicated as major catabolic regulator of bone mass in mice and humans. However, a potential involvement of other PPAR subtypes in the regulation of bone homeostasis has remained elusive. Here we report a previously unrecognized role of PPARβ/δ as a key regulator of bone turnover and the crosstalk between osteoblasts and osteoclasts. In contrast to activation of PPARγ, activation of PPARβ/δ amplified Wnt-dependent and β-catenin-dependent signaling and gene expression in osteoblasts, resulting in increased expression of osteoprotegerin (OPG) and attenuation of osteoblast-mediated osteoclastogenesis. Accordingly, PPARβ/δ-deficient mice had lower Wnt signaling activity, lower serum concentrations of OPG, higher numbers of osteoclasts and osteopenia. Pharmacological activation of PPARβ/δ in a mouse model of postmenopausal osteoporosis led to normalization of the altered ratio of tumor necrosis factor superfamily, member 11 (RANKL, also called TNFSF11) to OPG, a rebalancing of bone turnover and the restoration of normal bone density. Our findings identify PPARβ/δ as a promising target for an alternative approach in the treatment of osteoporosis and related diseases.
Pubmed
Web of science
Création de la notice
06/06/2013 19:02
Dernière modification de la notice
03/03/2018 18:28
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