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

Masaki Arioka, Fumi Takahashi-Yanaga, Masanori Sasaki, Tatsuya Yoshihara, Sachio Morimoto, Akihiko Takashima, Yoshihide Mori, Toshiyuki Sasaguri

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)677-682
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume440
Issue number4
DOIs
Publication statusPublished - Nov 1 2013

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Glycogen Synthase Kinase 3
Catenins
Wnt Signaling Pathway
Bone Regeneration
Bone Development
Bone
Bone and Bones
X-Ray Microtomography
Cyclin D1
Thigh
Ambulatory Surgical Procedures
Osteogenesis
Bone Marrow Cells
Bone Density
Femur
Surgery
Tomography
Minerals
Transcription Factors
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β. / Arioka, Masaki; Takahashi-Yanaga, Fumi; Sasaki, Masanori; Yoshihara, Tatsuya; Morimoto, Sachio; Takashima, Akihiko; Mori, Yoshihide; Sasaguri, Toshiyuki.

In: Biochemical and Biophysical Research Communications, Vol. 440, No. 4, 01.11.2013, p. 677-682.

Research output: Contribution to journalArticle

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