ERRα induces mitochondrial glutaminase expression guiding anaplerosis upon osteogenic differentiation of mesenchymal stem cells

5^th International Conference and Exhibition on Metabolomics

May 16-18, 2016 Osaka, Japan

Min Guan

CAS-Shenzhen Institutes of Advanced Technology, China

Scientific Tracks Abstracts: Metabolomics

Abstract :

Aging deteriorates osteogenic capacity of mesenchymal stem/stromal cells (MSCs), contributing to imbalanced bone remodeling and osteoporosis. Glutaminase (Gls) catabolizes glutamine into glutamate at the first step of mitochondrial glutaminedependent anaplerosis which is essential for MSCs upon osteogenic differentiation. Estrogen-related receptor �± (ERR�±) regulates genes required for mitochondrial function. Here, we found that ERR�± and Gls are up-regulated by osteogenic induction in human MSCs (hMSCs). In contrast, bone mass, osteogenic differentiation capacity of MSCs, ERR�±, Gls and osteogenic marker genes are significantly reduced with age. We demonstrated that ERR�± binds to response elements on Gls promoter and affects glutamine anaplerosis through transcriptional induction of Gls. Conversely, ERR�± inverse agonist compound 29 or mTOR inhibitor rapamycin significantly decreased expression levels of ERR�± and Gls, leading to deteriorated osteogenic differentiation of hMSCs. Importantly, overexpression of ERR�± in hMSCs promoted osteogenic differentiation and partially restored impairment by rapamycin. Finally, we proved that compensated ERR�± expression indeed potentiated osteogenesis capability of elderly mice MSCs in vitro. Together, we establish that Gls is a novel ERR�± target gene and ERR�±/Gls signaling pathway plays an important role in osteogenic differentiation of MSCs. Our findings suggest that restoring age-related mitochondrial glutamine-dependent anaplerosis may be beneficial for osteoporosis.

Biography :

Min Guan received her PhD degree from Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences in 2009. She performed Postdoctoral studies at University of California and Johns Hopkins Medical School, USA. She was appointed as Associate Professor at Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences in 2013. She focuses on studying mechanisms of metabolic diseases, and has published in reputed journals including Nature medicine, Hepatology and Stem cells.

Email: min.guan@siat.ac.cn