Scholtysek C, Katzenbeisser J, Fu H, Uderhardt S, Ipseiz N, Stoll C, Zaiss M, Stock M, Donhauser LR, Boehm C, Kleyer A, Heß A, Engelke K, David JP, Djouad F, Tuckermann JP, Desvergne B, Schett G, Krönke G (2013)
Publication Type: Journal article
Publication year: 2013
Book Volume: 19
Pages Range: 608-13
Journal Issue: 5
DOI: 10.1038/nm.3146
Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis. Furthermore, PPAR? 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 PPAR?/? as a key regulator of bone turnover and the crosstalk between osteoblasts and osteoclasts. In contrast to activation of PPAR?, activation of PPAR?/? amplified Wnt-dependent and ?-catenin-dependent signaling and gene expression in osteoblasts, resulting in increased expression of osteoprotegerin (OPG) and attenuation of osteoblast-mediated osteoclastogenesis. Accordingly, PPAR?/?-deficient mice had lower Wnt signaling activity, lower serum concentrations of OPG, higher numbers of osteoclasts and osteopenia. Pharmacological activation of PPAR?/? 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 PPAR?/? as a promising target for an alternative approach in the treatment of osteoporosis and related diseases.
APA:
Scholtysek, C., Katzenbeisser, J., Fu, H., Uderhardt, S., Ipseiz, N., Stoll, C.,... Krönke, G. (2013). PPARβ/δ governs Wnt signaling and bone turnover. Nature Medicine, 19(5), 608-13. https://doi.org/10.1038/nm.3146
MLA:
Scholtysek, Carina, et al. "PPARβ/δ governs Wnt signaling and bone turnover." Nature Medicine 19.5 (2013): 608-13.
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