Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

Glycogen synthase kinase (GSK)-3 beta plays an important role in osteoblastogenesis by regulating the Wnt/beta-catenin signaling pathway. Therefore, we investigated whether GSK-3 beta deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3 beta (GSK-3 beta(+/-)). The amounts of beta-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3 beta(+/-) mice were significantly increased compared with those of wild-type mice, indicating that Wnt/beta-catenin signals were enhanced in GSK-3 beta(+/-) mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3 beta(+/-) mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3 beta deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3 beta(+/-) mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3 beta, probably through activation of the Wnt/beta-catenin signaling pathway. (C) 2013 Elsevier Inc. All rights reserved.