title: Genetic deletion of catalytic subunits of AMP-activated protein kinase increases osteoclasts and reduces bone mass in young adult mice.
abstract: 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 AMPKα1 (Prkaa1(-/-)) or AMPKα2 (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 AMPKα2 KO-induced bone mass reduction was largely attributable to elevated bone resorption. In agreement with our in vivo results, AMPKα deficiency was associated with increased osteoclastogenesis in vitro. Moreover, we found that AMPKα1 inhibited the receptor activator of nuclear factor κB (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.
authors.affiliation: Department of Pharmacology and Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, Connecticut 06520, USA. heeseog.kang@yale.edu
authors.forename: Heeseog
authors.initials: H
authors.lastname: Kang
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Dianqing
authors.initials: D
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000235:genetics; D010010:Osteoclasts / Q000201:enzymology* / Q000473:pathology; D010012:Osteogenesis; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases