Publication in detail

FASEB J 2010 Jan;24(1):275-85. Epub 2009 Se

Germline deletion of AMP-activated protein kinase {beta} subunits reduces bone mass without altering osteoclast differentiation or function.

Gillespie, MT; Kemp, BE; McGregor, NE; Poulton, IJ; Quinn, JM; Saleh, H; Scott, JW; Sims, NA; Tam, S; van, Denderen BJ.

Prince Henry's Institute, Monash Medical Centre, Clayton, Australia.

Since AMP-activated protein kinase (AMPK) plays important roles in modulating metabolism in response to diet and exercise, both of which influence bone mass, we examined the influence of AMPK on bone mass in mice. AMPK is an alphabetagamma heterotrimer where the beta subunit anchors the alpha catalytic and gamma regulatory subunits. Germline deletion of either AMPK beta1 or beta2 subunit isoforms resulted in reduced trabecular bone density and mass, but without effects on osteoclast (OC) or osteoblast (OB) numbers, as compared to wild-type littermate controls. We tested whether activating AMPK in vivo would enhance bone density but found AICA-riboside treatment caused a profound loss of trabecular bone volume (49.5%) and density and associated increased OC numbers. Consistent with this, AICA-riboside strongly stimulated OC differentiation in vitro, in an adenosine kinase-dependent manner. OCs and macrophages (unlike OBs) lacked AMPK beta2 subunit expression, and when generated from AMPK beta1(-/-) mice displayed no detectable AMPK activity. Nevertheless, AICA-riboside was equally effective at stimulating OC differentiation from wild-type or beta1(-/-) progenitors, indicating that AMPK is not essential for OC differentiation or the stimulatory action of AICA-riboside. These results show that AMPK is required to maintain normal bone density, but not through bone cell differentiation, and does not mediate powerful osteolytic effects of AICA-riboside.

ยป Online Version

Proven Track Record

The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 400 scientific publications are based on research using Ozgene mice.

Go to Publications

Global Client Base

Ozgene generates genetically customised mice for researchers around the world. Ozgene mice can be found in 31 different countries on 5 continents from small academic institutions to multinational pharmaceutical companies.

See Client Papers

Lean Management

Ozgene is applying Lean Management principles to deliver the highest quality services and shortest lead times to our customers. The implementation of Lean Culture has already seen an improvement in our processes and timelines.

Read More