| First Author | Kang H | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 17 | Pages | 12187-96 |
| PubMed ID | 23486478 | Mgi Jnum | J:198388 |
| Mgi Id | MGI:5496494 | Doi | 10.1074/jbc.M112.430389 |
| Citation | Kang H, et al. (2013) Genetic deletion of catalytic subunits of AMP-activated protein kinase increases osteoclasts and reduces bone mass in young adult mice. J Biol Chem 288(17):12187-96 |
| abstractText | AMP-activated protein kinase (AMPK) is a key regulator of cellular and systemic energy homeostasis and a potential therapeutic target for the intervention of cancer and metabolic disorders. However, the role of AMPK in bone homeostasis remains incompletely understood. Here we assessed the skeletal phenotype of mice lacking catalytic subunits of AMPK and found that mice lacking AMPKalpha1 (Prkaa1(-/-)) or AMPKalpha2 (Prkaa2(-/-)) had reduced bone mass compared with the WT mice, although the reduction was less in Prkaa2(-/-) mice than in Prkaa1(-/-) mice. Static and dynamic bone histomorphometric analyses revealed that Prkaa1(-/-) mice had an elevated rate of bone remodeling because of increases in bone formation and resorption, whereas AMPKalpha2 KO-induced bone mass reduction was largely attributable to elevated bone resorption. In agreement with our in vivo results, AMPKalpha deficiency was associated with increased osteoclastogenesis in vitro. Moreover, we found that AMPKalpha1 inhibited the receptor activator of nuclear factor kappaB (RANK) signaling, providing an explanation for AMPK-mediated inhibition of osteoclastogenesis. Therefore, our findings further underscore the importance of AMPK in bone homeostasis, in particular osteoclastogenesis, in young adult mammals. |
