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PPARβ/δ governs Wnt signaling and bone turnover

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PPARβ/δ governs Wnt signaling and bone turnover. / 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.

in: NAT MED, Jahrgang 19, Nr. 5, 01.05.2013, S. 608-13.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Scholtysek, C, Katzenbeisser, J, Fu, H, Uderhardt, S, Ipseiz, N, Stoll, C, Zaiss, MM, Stock, M, Donhauser, L, Böhm, C, Kleyer, A, Hess, A, Engelke, K, David, J-P, Djouad, F, Tuckermann, JP, Desvergne, B, Schett, G & Krönke, G 2013, 'PPARβ/δ governs Wnt signaling and bone turnover', NAT MED, Jg. 19, Nr. 5, S. 608-13. https://doi.org/10.1038/nm.3146

APA

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. (2013). PPARβ/δ governs Wnt signaling and bone turnover. NAT MED, 19(5), 608-13. https://doi.org/10.1038/nm.3146

Vancouver

Scholtysek C, Katzenbeisser J, Fu H, Uderhardt S, Ipseiz N, Stoll C et al. PPARβ/δ governs Wnt signaling and bone turnover. NAT MED. 2013 Mai 1;19(5):608-13. https://doi.org/10.1038/nm.3146

Bibtex

@article{39da195d4b24481f8c4eebc92b7d81df,
title = "PPARβ/δ governs Wnt signaling and bone turnover",
abstract = "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.",
keywords = "Alleles, Animals, Bone Diseases, Metabolic, Bone Resorption, Bone and Bones, Female, Glucose, Mice, Mice, Inbred C57BL, Mice, Knockout, Osteoblasts, Osteoclasts, Osteoprotegerin, PPAR delta, PPAR-beta, RANK Ligand, Time Factors, Wnt Proteins, Wnt Signaling Pathway, beta Catenin",
author = "Carina Scholtysek and Julia Katzenbeisser and He Fu and Stefan Uderhardt and Natacha Ipseiz and Cornelia Stoll and Zaiss, {Mario M} and Michael Stock and Laura Donhauser and Christina B{\"o}hm and Arnd Kleyer and Andreas Hess and Klaus Engelke and Jean-Pierre David and Farida Djouad and Tuckermann, {Jan Peter} and B{\'e}atrice Desvergne and Georg Schett and Gerhard Kr{\"o}nke",
year = "2013",
month = may,
day = "1",
doi = "10.1038/nm.3146",
language = "English",
volume = "19",
pages = "608--13",
journal = "NAT MED",
issn = "1078-8956",
publisher = "NATURE PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - PPARβ/δ governs Wnt signaling and bone turnover

AU - Scholtysek, Carina

AU - Katzenbeisser, Julia

AU - Fu, He

AU - Uderhardt, Stefan

AU - Ipseiz, Natacha

AU - Stoll, Cornelia

AU - Zaiss, Mario M

AU - Stock, Michael

AU - Donhauser, Laura

AU - Böhm, Christina

AU - Kleyer, Arnd

AU - Hess, Andreas

AU - Engelke, Klaus

AU - David, Jean-Pierre

AU - Djouad, Farida

AU - Tuckermann, Jan Peter

AU - Desvergne, Béatrice

AU - Schett, Georg

AU - Krönke, Gerhard

PY - 2013/5/1

Y1 - 2013/5/1

N2 - 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.

AB - 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.

KW - Alleles

KW - Animals

KW - Bone Diseases, Metabolic

KW - Bone Resorption

KW - Bone and Bones

KW - Female

KW - Glucose

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Osteoblasts

KW - Osteoclasts

KW - Osteoprotegerin

KW - PPAR delta

KW - PPAR-beta

KW - RANK Ligand

KW - Time Factors

KW - Wnt Proteins

KW - Wnt Signaling Pathway

KW - beta Catenin

U2 - 10.1038/nm.3146

DO - 10.1038/nm.3146

M3 - SCORING: Journal article

C2 - 23542786

VL - 19

SP - 608

EP - 613

JO - NAT MED

JF - NAT MED

SN - 1078-8956

IS - 5

ER -