| First Author | Scholtysek C | Year | 2013 |
| Journal | Nat Med | Volume | 19 |
| Issue | 5 | Pages | 608-13 |
| PubMed ID | 23542786 | Mgi Jnum | J:198360 |
| Mgi Id | MGI:5496466 | Doi | 10.1038/nm.3146 |
| Citation | Scholtysek C, et al. (2013) PPARbeta/delta governs Wnt signaling and bone turnover. Nat Med 19(5):608-13 |
| abstractText | Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis. Furthermore, PPARgamma 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 PPARbeta/delta as a key regulator of bone turnover and the crosstalk between osteoblasts and osteoclasts. In contrast to activation of PPARgamma, activation of PPARbeta/delta amplified Wnt-dependent and beta-catenin-dependent signaling and gene expression in osteoblasts, resulting in increased expression of osteoprotegerin (OPG) and attenuation of osteoblast-mediated osteoclastogenesis. Accordingly, PPARbeta/delta-deficient mice had lower Wnt signaling activity, lower serum concentrations of OPG, higher numbers of osteoclasts and osteopenia. Pharmacological activation of PPARbeta/delta 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 PPARbeta/delta as a promising target for an alternative approach in the treatment of osteoporosis and related diseases. |
