Details

Autor(en) / Beteiligte

• Scholtysek, Carina
• Katzenbeisser, Julia
• Fu, He
• Uderhardt, Stefan
• Ipseiz, Natacha
• Stoll, Cornelia
• Zaiss, Mario M
• Stock, Michael
• Donhauser, Laura
• Böhm, Christina
• Kleyer, Arnd
• Hess, Andreas
• Engelke, Klaus
• David, Jean-Pierre
• Djouad, Farida
• Tuckermann, Jan Peter
• Desvergne, Béatrice
• Schett, Georg
• Krönke, Gerhard

Titel

PPARβ/δ governs Wnt signaling and bone turnover

Ist Teil von

• Nature medicine, 2013-05, Vol.19 (5), p.608-613

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Gerhard Krönke and his colleagues show that PPARβ/δ regulates Wnt signaling in osteoblasts, which in turn determines the proper ratio of OPG to RANKL and thus bone homeostasis. They go on to show that pharmacological activation of this receptor normalizes bone density in a mouse model of osteoporosis. Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis 1 . Furthermore, PPARγ has been implicated as major catabolic regulator of bone mass in mice and humans 2 , 3 , 4 , 5 . 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.