Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Oral and Maxillofacial Surgery, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Biochem Biophys Res Commun. 2013 Nov 1;440(4):677-82. doi: 10.1016/j.bbrc.2013.09.126. Epub 2013 Oct 4.
Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β(+/-)). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β(+/-) mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β(+/-) mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β(+/-) mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β 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-3β(+/-) mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.
糖原合酶激酶（GSK）-3β 通过调节 Wnt/β-连环蛋白信号通路在成骨细胞分化中发挥重要作用。因此，我们使用杂合缺失 GSK-3β 的小鼠（GSK-3β(+/-)）来研究 GSK-3β 缺乏是否会影响骨骼发育和再生。与野生型小鼠相比，GSK-3β(+/-) 小鼠骨髓细胞中的 β-连环蛋白、c-Myc、细胞周期蛋白 D1 和 runt 相关转录因子-2（Runx2）的含量显著增加，表明 Wnt/β-连环蛋白信号在 GSK-3β(+/-) 小鼠中增强。对股骨远端干骺端的微计算机断层扫描显示，与野生型小鼠相比，GSK-3β(+/-) 小鼠的皮质骨和松质骨体积均增加。随后，为了研究 GSK-3β 缺乏对骨再生的影响，我们在股骨中建立了部分骨缺损，并在手术后 14 天观察新骨。与野生型小鼠相比，GSK-3β(+/-) 小鼠的新骨体积和矿物质密度明显更高。这些结果表明，通过抑制 GSK-3β，体内的骨形成和再生被加速，可能是通过激活 Wnt/β-连环蛋白信号通路。
