Functional differences between AMPK α1 and α2 subunits in osteogenesis, osteoblast-associated induction of osteoclastogenesis, and adipogenesis.
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.
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Yu-Gang
YG
Wang
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Xiu-Guo
XG
Han
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Ying
Y
Yang
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Han
H
Qiao
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Ke-Rong
KR
Dai
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Qi-Ming
QM
Fan
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People's Republic of China.
Ting-Ting
TT
Tang
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002478:Cells, Cultured; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D011944:Receptors, Androgen / Q000378:metabolism
C000607144:AR protein, mouse; D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D008562:Membrane Glycoproteins; D011944:Receptors, Androgen; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases