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 lit- termate. 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.

Deletion of the Transcription Factor PGC-1α in Mice Negatively Regulates Bone Mass / Colaianni, Graziana; Lippo, Luciana; Sanesi, Lorenzo; Brunetti, Giacomina; Celi, Monica; Cirulli, Nunzio; Passeri, Giovanni; Reseland, Janne; Schipani, Ernestina; Felicia Faienza, Maria; Tarantino, Umberto; Colucci, Silvia; Grano, Maria. - In: CALCIFIED TISSUE INTERNATIONAL. - ISSN 0171-967X. - 103:6(2018), pp. 638-652. [10.1007/s00223-018-0459-4]

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

Giovanni Passeri;
2018

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 lit- termate. 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.
Deletion of the Transcription Factor PGC-1α in Mice Negatively Regulates Bone Mass / Colaianni, Graziana; Lippo, Luciana; Sanesi, Lorenzo; Brunetti, Giacomina; Celi, Monica; Cirulli, Nunzio; Passeri, Giovanni; Reseland, Janne; Schipani, Ernestina; Felicia Faienza, Maria; Tarantino, Umberto; Colucci, Silvia; Grano, Maria. - In: CALCIFIED TISSUE INTERNATIONAL. - ISSN 0171-967X. - 103:6(2018), pp. 638-652. [10.1007/s00223-018-0459-4]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2850839
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