Inhibition of GSK-3β increases trabecular bone volume but not cortical bone volume in adenine-induced uremic mice with severe hyperparathyroidism

Narihito Tatsumoto, masaki arioka, Shunsuke Yamada, Fumi Takahashi, Masanori Tokumoto, Kazuhiko Tsuruya, Takanari Kitazono, Toshiyuki Sasaguri

Research output: Contribution to journalArticle

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Abstract

Patients with chronic kidney disease (CKD) are at increased risk for bone fractures compared with the general population. Repression of the Wnt/bcatenin signaling pathway is associated with bone abnormalities. Inhibition of glycogen synthase kinase (GSK)-3β, a critical component of the Wnt/β-catenin signaling pathway, increases bone volume through accumulation of β-catenin. It remains unknown whether inhibition of GSK-3β increases bone volume in CKD. The present in vivo study examined the effects of GSK-3β inhibition on bone volume in CKD mice. Wild-type mice were divided into three groups. One group was fed a control diet (CNT) and the other two groups were fed a diet containing 0.2% adenine and given water with or without lithium chloride (LiCl), a GSK-3 inhibitor (CKD, CKD+LiCl, respectively). GSK-3β heterozygous knockout mice were fed a diet containing 0.2% adenine (CKDGSK- 3β+/-). After 6 weeks, trabecular and cortical bone volumes of the femur were analyzed using microcomputed tomography. CKD mice developed azotemia, hyperphosphatemia, and hyperparathyroidism, followed by a decrease in cortical bone volume without any change in trabecular bone volume. Serum levels of urea nitrogen, phosphate, and parathyroid hormone were comparable among the three groups of CKD mice. Trabecular bone volume increased in CKD-GSK-3β+/- and CKD+LiCl mice compared with CNT and CKD mice. However, there were no significant differences in cortical bone volume among the three groups of CKD mice. The results suggest that inhibition of GSK-3β increases trabecular bone volume but not cortical bone volume in adenineinduced uremic mice with uncontrolled hyperparathyroidism.

Original languageEnglish
Article numbere13010
JournalPhysiological Reports
Volume4
Issue number21
DOIs
Publication statusPublished - Nov 1 2016

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Glycogen Synthase Kinase 3
Hyperparathyroidism
Adenine
Chronic Renal Insufficiency
Lithium Chloride
Diet
Bone and Bones
Catenins
Wnt Signaling Pathway
Cancellous Bone
Cortical Bone
Hyperphosphatemia
Azotemia
X-Ray Microtomography
Bone Fractures
Parathyroid Hormone
Knockout Mice
Femur
Urea
Nitrogen

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

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Inhibition of GSK-3β increases trabecular bone volume but not cortical bone volume in adenine-induced uremic mice with severe hyperparathyroidism. / Tatsumoto, Narihito; arioka, masaki; Yamada, Shunsuke; Takahashi, Fumi; Tokumoto, Masanori; Tsuruya, Kazuhiko; Kitazono, Takanari; Sasaguri, Toshiyuki.

In: Physiological Reports, Vol. 4, No. 21, e13010, 01.11.2016.

Research output: Contribution to journalArticle

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