51. The Novel Role of PGC1α in Bone Metabolism
- Author
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P Pignataro, Manuela Dicarlo, Maria Grano, Cinzia Buccoliero, Francesco Gaccione, Graziana Colaianni, and Silvia Colucci
- Subjects
0301 basic medicine ,Bone disease ,QH301-705.5 ,Adipose tissue ,Review ,Mitochondrion ,Osteocytes ,Catalysis ,Bone and Bones ,Bone remodeling ,Inorganic Chemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Osteogenesis ,Sirtuin 3 ,Coactivator ,medicine ,Animals ,Humans ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Gene knockdown ,Organelle Biogenesis ,Osteoblasts ,biology ,Chemistry ,Organic Chemistry ,Cell Differentiation ,General Medicine ,medicine.disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Computer Science Applications ,Cell biology ,Mitochondria ,030104 developmental biology ,Mitochondrial biogenesis ,Sirtuin ,biology.protein ,bone metabolism ,metabolic regulations ,030217 neurology & neurosurgery ,Signal Transduction ,Transcription Factors - Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. Furthermore, in a mouse model of bone disease, PGC1α activation stimulates osteoblastic gene expression and inhibits atrogene transcription. PGC1α overexpression positively affects the activity of Sirtuin 3, a mitochondrial nicotinammide adenina dinucleotide (NAD)-dependent deacetylase, on osteoblastic differentiation. In vitro, PGC1α overexpression prevents the reduction of mitochondrial density, membrane potential and alkaline phosphatase activity caused by Sirtuin 3 knockdown in osteoblasts. Moreover, PGC1α influences the commitment of skeletal stem cells towards an osteogenic lineage, while negatively affects marrow adipose tissue accumulation. In this review, we will focus on recent findings about PGC1α action on bone metabolism, in vivo and in vitro, and in pathologies that cause bone loss, such as osteoporosis and type 2 diabetes.
- Published
- 2021