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 α has two isoforms, it is unclear whether functional differences between them exist in the skeletal system. The current study overexpressed AMPKα1 and α2 in MC3T3-E1 cells, primary osteoblasts and mouse BMSCs by lentiviral transduction. Cells overexpressing AMPKα2 showed higher osteogenesis potential than AMPKα1, wherein androgen receptor (AR) and osteoactivin played important roles. RANKL and M-CSF were secreted at lower levels from cells overexpressing α2 than α1, resulting in decreased osteoblast-associated osteoclastogenesis. Adipogenesis was inhibited to a greater degree in 3T3-L1 cells overexpressing α2 than α1, which was modulated by AR. An abnormal downregulation of AMPKα2 was observed in human BMSCs exhibiting the fibrous dysplasia (FD) phenotype. Overexpression of AMPKα2 in these cells rescued the defect in osteogenesis, suggesting that AMPKα2 plays a role in FD pathogenesis. These findings highlight functional differences between AMPKα1 and α2, and provide a basis for investigating the molecular mechanisms of diseases associated with impaired functioning of the skeletal system.
Highlights
Several important hormones secreted by bone cells regulate energy balance and mineral ion homeostasis
The present study investigated whether functional differences exist between AMPK α1 and α2 subunits with respect to osteogenesis, osteoblast-associated induction of osteoclastogenesis, and adipogenesis
The results indicated that the subunit composition of AMPK determines the susceptibility of MC3T3-E1, 3T3-L1, primary osteoblasts and bone marrow stromal cells (BMSCs) to osteogenic, osteoclastogenic, and adipogenic induction, which involved androgen receptor (AR), osteoactivin, macrophage colony-stimulating factor (M-CSF), and receptor activator of nuclear factor κB ligand (RANKL)
Summary
Several important hormones secreted by bone cells regulate energy balance and mineral ion homeostasis. Appetite-stimulating neurons and the anorexigenic, appetite-suppressing neurons They encompass some of the most effective control of energy homeostasis in the entire body. The α1 subunit is widely expressed, whereas the α2 subunit is highly expressed in skeletal and cardiac muscle and in the liver[12]; a recent study showed that AMPK activation by electrical stimulation of rat hindlimb muscle involved the α2 isoform[13]. It is unclear whether the α1 and α2 isoforms have distinct biological functions in the skeletal system
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
