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09.08.2018 | Original Research

Deletion of the Transcription Factor PGC-1α in Mice Negatively Regulates Bone Mass

verfasst von: Graziana Colaianni, Luciana Lippo, Lorenzo Sanesi, Giacomina Brunetti, Monica Celi, Nunzio Cirulli, Giovanni Passeri, Janne Reseland, Ernestina Schipani, Maria Felicia Faienza, Umberto Tarantino, Silvia Colucci, Maria Grano

Erschienen in: Calcified Tissue International | Ausgabe 6/2018

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Abstract

Peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) is a transcription coactivator that interacts with a broad range of transcription factors involved in several biological responses. Here, we show that PGC1α plays a role in skeletal homeostasis since aged PGC1α-deficient mice (PGC1α^−/−) display impaired bone structure. Micro-CT of the tibial mid-shaft showed a marked decrease of cortical thickness in PGC1α^−/− (− 11.9%, p < 0.05) mice compared to wild-type littermate. Trabecular bone was also impaired in knock out mice which displayed lower trabecular thickness (Tb.Th) (− 5.9% vs PGC1α^+/+, p < 0.05), whereas trabecular number (Tb.N) was higher than wild-type mice (+ 72% vs PGC1α^+/+, p < 0.05), thus resulting in increased (+ 31.7% vs PGC1α^+/+, p < 0.05) degree of anisotropy (DA), despite unchanged bone volume fraction (BV/TV). Notably, these impairments of cortical and trabecular bone led to a dramatic ~ 48.4% decrease in bending strength (p < 0.01). These changes in PGC1α^−/− mice were paralleled by a significant increase in osteoclast number at the cortical bone surface and in serum level of the bone resorption marker, namely, C-terminal cross-linked telopeptides of type I collagen (CTX-I). We also found that in cortical bone, there was lower expression of mRNA codifying for the key bone-building protein Osteocalcin (Ocn). Interestingly, Collagen I mRNA expression was reduced in mesenchymal stem cells from bone marrow of PGC1α^−/−, thus indicating that differentiation of osteoblast lineage is downregulated. Overall, results presented herein suggest that PGC1α may play a key role in bone metabolism.

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Titel: Deletion of the Transcription Factor PGC-1α in Mice Negatively Regulates Bone Mass
verfasst von: Graziana Colaianni
Luciana Lippo
Lorenzo Sanesi
Giacomina Brunetti
Monica Celi
Nunzio Cirulli
Giovanni Passeri
Janne Reseland
Ernestina Schipani
Maria Felicia Faienza
Umberto Tarantino
Silvia Colucci
Maria Grano
Publikationsdatum: 09.08.2018
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 6/2018
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-018-0459-4

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Deletion of the Transcription Factor PGC-1α in Mice Negatively Regulates Bone Mass

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