Abstract
ackground As members of the nuclear receptor superfamily, peroxisome proliferator-activated receptors (PPARs) do not only act as central metabolic regulators but simultaneously orchestrate the inflammatory response and bone homeostasis. However, underlying mechanisms are incompletely understood.Objectives Here we aimed to study the role of the nuclear receptor PPARdelta in bone biology and during the regulation of energy homeostasis by the skeleton.Methods We analysed the involvement of PPARdelta in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Furthermore, we generated mice with a conditional deletion of PPARdelta in osteoblasts by crossing animals carrying floxed alleles of PPARdelta with mice expressing a Cre recombinase under the Runx2 promoter.Results We observed a robust induction of the expression of PPARdelta during the differentiation of MSCs into osteoblasts, whereas PPARgamma was downregulated. Notably, deletion of PPARdelta in MSCs resulted in an impaired differentiation of osteoblasts. Mice carrying a conditional deletion of PPARdelta in pre-osteoblasts showed reduced numbers of osteocytes, osteopenia and developed insulin resistence.Conclusions Our data demonstrates a crucial role of PPARdelta in the differentiation of osteoblasts and identifies this nuclear receptor as an important factor mediating the crosstalk between systemic energy homeostasis and the skeleton.