Abstract：
:Inhibition of glycogen synthase kinase (GSK)-3 and the consequent activation of the Wnt/β-catenin signaling pathway have been reported to increase bone volume. To develop a novel pharmacotherapy for injured bone, we investigated whether GSK-3 inhibitor was effective in promoting bone formation. In in vitro experiments, we examined the effects of GSK-3 inhibitors LiCl and SB216763 on osteoblastogenesis of mesenchymal progenitor C3H10T1/2 cells and osteoclastogenesis of osteoclast precursor RAW-D cells. Both inhibitors promoted osteoblast differentiation, assessed by alkaline phosphatase activity and calcium deposition, stimulating the Wnt/β-catenin signaling pathway and thereby inducing Runx2. On the other hand, the GSK-3 inhibitors suppressed osteoclast differentiation, assessed by tartrate-resistant acid phosphatase staining and number of nuclei in the cells, reducing NFATc1 expression independently of the Wnt/β-catenin signaling pathway. In subsequently performed in vivo studies, we examined the effect of locally administered Li2CO3 on the recovery from a partial defect made on the rat tibia. Computerized tomography and bone histomorphometry showed that Li2CO3 accelerated bone regeneration in defect lesion with increased lamellar bone ratio compared with the controls. These results suggested that local application of lithium (or other GSK-3 inhibitors) might effectively facilitate recovery from bone injury by promoting osteoblastogenesis and inhibiting osteoclastogenesis.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Arioka M,Takahashi-Yanaga F,Sasaki M,Yoshihara T,Morimoto S,Hirata M,Mori Y,Sasaguri Tdoi
10.1016/j.bcp.2014.06.011subject
Has Abstractpub_date
2014-08-15 00:00:00pages
397-405issue
4eissn
0006-2952issn
1873-2968pii
S0006-2952(14)00354-2journal_volume
90pub_type
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journal_title：Biochemical pharmacology
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更新日期：2015-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2006-05-28 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2002-03-15 00:00:00
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pub_type： 杂志文章
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更新日期：1998-11-01 00:00:00
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更新日期：2013-05-15 00:00:00
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pub_type： 杂志文章
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更新日期：1993-11-02 00:00:00
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pub_type： 杂志文章
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更新日期：1990-02-01 00:00:00
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journal_title：Biochemical pharmacology
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更新日期：2003-09-15 00:00:00
