TI - GSK-3beta Controls Osteogenesis through Regulating Runx2 Activity GSK-3beta Regulates Osteogenesis . AB - Despite accumulated knowledge of various signalings regulating bone formation , the molecular network has not been clarified sufficiently to lead to clinical application . Here we show that heterozygous glycogen synthase kinase-3beta ( GSK-3beta ) -deficient mice displayed an increased bone formation due to an enhanced transcriptional activity of Runx2 by suppressing the inhibitory PHOSphorylation at a specific site . The cleidocranial dysplasia in heterozygous Runx2-deficient mice was significantly rescued by the genetic insufficiency of GSK-3beta or the oral administration of lithium chloride , a selective inhibitor of GSK-3beta . These results establish GSK-3beta as a key attenuator of Runx2 activity in bone formation and as a potential molecular target for clinical treatment of bone catabolic disorders like cleidocranial dysplasia .