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PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass

Müller, Dorothea I. H., Stoll, Cornelia, Palumbo-Zerr, Katrin, Böhm, Christina, Krishnacoumar, Brenda, Ipseiz, Natacha, Taubmann, Jule, Zimmermann, Max, Böttcher, Martin, Mougiakakos, Dimitrios, Tuckermann, Jan, Djouad, Farida, Schett, Georg, Scholtysek, Carina and Krönke, Gerhard 2020. PPARδ-mediated mitochondrial rewiring of osteoblasts determines bone mass. Scientific Reports 10 , 8428. 10.1038/s41598-020-65305-5

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Abstract

Bone turnover, which is determined by osteoclast-mediated bone resorption and osteoblast-mediated bone formation, represents a highly energy consuming process. The metabolic requirements of osteoblast differentiation and mineralization, both essential for regular bone formation, however, remain incompletely understood. Here we identify the nuclear receptor peroxisome proliferator-activated receptor (PPAR) δ as key regulator of osteoblast metabolism. Induction of PPARδ was essential for the metabolic adaption and increased rate in mitochondrial respiration necessary for the differentiation and mineralization of osteoblasts. Osteoblast-specific deletion of PPARδ in mice, in turn, resulted in an altered energy homeostasis of osteoblasts, impaired mineralization and reduced bone mass. These data show that PPARδ acts as key regulator of osteoblast metabolism and highlight the relevance of cellular metabolic rewiring during osteoblast-mediated bone formation and bone-turnover.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 10 June 2020
Date of Acceptance: 27 April 2020
Last Modified: 11 Jun 2020 12:00
URI: http://orca-mwe.cf.ac.uk/id/eprint/132309

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