Functional differences between AMPK ?1 and ?2 subunits in osteogenesis, osteoblast-associated induction of osteoclastogenesis, and adipogenesis.

ABSTRACT: The endocrine role of the skeleton-which is impaired in human diseases including osteoporosis, obesity and diabetes-has been highlighted previously. In these diseases, the role of AMPK, a sensor and regulator of energy metabolism, is of biological and clinical importance. Since AMPK's main catalytic subunit ? has two isoforms, it is unclear whether functional differences between them exist in the skeletal system. The current study overexpressed AMPK?1 and ?2 in MC3T3-E1 cells, primary osteoblasts and mouse BMSCs by lentiviral transduction. Cells overexpressing AMPK?2 showed higher osteogenesis potential than AMPK?1, wherein androgen receptor (AR) and osteoactivin played important roles. RANKL and M-CSF were secreted at lower levels from cells overexpressing ?2 than ?1, resulting in decreased osteoblast-associated osteoclastogenesis. Adipogenesis was inhibited to a greater degree in 3T3-L1 cells overexpressing ?2 than ?1, which was modulated by AR. An abnormal downregulation of AMPK?2 was observed in human BMSCs exhibiting the fibrous dysplasia (FD) phenotype. Overexpression of AMPK?2 in these cells rescued the defect in osteogenesis, suggesting that AMPK?2 plays a role in FD pathogenesis. These findings highlight functional differences between AMPK?1 and ?2, and provide a basis for investigating the molecular mechanisms of diseases associated with impaired functioning of the skeletal system.

SUBMITTER: Wang YG 

PROVIDER: S-EPMC5013406 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature