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

被引:34
作者
Arioka, Masaki [1 ,2 ]
Takahashi-Yanaga, Fumi [1 ,3 ]
Sasaki, Masanori [2 ]
Yoshihara, Tatsuya [1 ]
Morimoto, Sachio [1 ]
Takashima, Akihiko [4 ]
Mori, Yoshihide [2 ]
Sasaguri, Toshiyuki [1 ]
机构
[1] Kyushu Univ, Fac Med Sci, Dept Clin Pharmacol, Fukuoka 8128582, Japan
[2] Kyushu Univ, Fac Dent Sci, Dept Oral & Maxillofacial Surg, Fukuoka 8128582, Japan
[3] Kyushu Univ, Fac Med Sci, Global Med Sci Educ Unit, Fukuoka 8128582, Japan
[4] Natl Ctr Geriatr & Gerontol, Dept Aging Neurobiol, Oobu, Japan
关键词
Bone regeneration; GSK-3; beta; Wnt/beta-catenin signaling pathway; OSTEOBLAST DIFFERENTIATION; IN-VIVO; MASS; EXPRESSION; LRP5; OSTEOGENESIS; ACTIVATOR; DISEASE; CBFA1; CELLS;
D O I
10.1016/j.bbrc.2013.09.126
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:677 / 682
页数:6
相关论文
共 27 条
[1]   Activated β-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction [J].
Bain, G ;
Müller, T ;
Wang, X ;
Papkoff, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 301 (01) :84-91
[2]   Guidelines for Assessment of Bone Microstructure in Rodents Using Micro-Computed Tomography [J].
Bouxsein, Mary L. ;
Boyd, Stephen K. ;
Christiansen, Blaine A. ;
Guldberg, Robert E. ;
Jepsen, Karl J. ;
Mueller, Ralph .
JOURNAL OF BONE AND MINERAL RESEARCH, 2010, 25 (07) :1468-1486
[3]   Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice [J].
Clément-Lacroix, P ;
Ai, MR ;
Morvan, F ;
Roman-Roman, S ;
Vayssière, B ;
Belleville, C ;
Estrera, K ;
Warman, ML ;
Baron, R ;
Rawadi, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (48) :17406-17411
[4]   Functional redundancy of GSK-3α and GSK-3β in Wnt/β-catenin signaling shown by using an allelic series of embryonic stem cell lines [J].
Doble, Bradley W. ;
Patel, Satish ;
Wood, Geoffrey A. ;
Kockeritz, Lisa K. ;
Woodgett, James R. .
DEVELOPMENTAL CELL, 2007, 12 (06) :957-971
[5]   Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation [J].
Ducy, P ;
Zhang, R ;
Geoffroy, V ;
Ridall, AL ;
Karsenty, G .
CELL, 1997, 89 (05) :747-754
[6]   GSK-3 inhibitors: preclinical and clinical focus on CNS [J].
Eldar-Finkelman, Hagit ;
Martinez, Ana .
FRONTIERS IN MOLECULAR NEUROSCIENCE, 2011, 4
[7]   Glycogen Synthase Kinase-3α/β Inhibition Promotes In Vivo Amplification of Endogenous Mesenchymal Progenitors With Osteogenic and Adipogenic Potential and Their Differentiation to the Osteogenic Lineage [J].
Gambardella, Alessandra ;
Nagaraju, Chandan K. ;
O'Shea, Patrick J. ;
Mohanty, Sindhu T. ;
Kottam, Lucksy ;
Pilling, James ;
Sullivan, Michael ;
Djerbi, Mounira ;
Koopmann, Witte ;
Croucher, Peter I. ;
Bellantuono, Ilaria .
JOURNAL OF BONE AND MINERAL RESEARCH, 2011, 26 (04) :811-821
[8]   Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression [J].
Gaur, T ;
Lengner, CJ ;
Hovhannisyan, H ;
Bhat, RA ;
Bodine, PVN ;
Komm, BS ;
Javed, A ;
van Wijnen, AJ ;
Stein, JL ;
Stein, GS ;
Lian, JB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (39) :33132-33140
[9]   LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development [J].
Gong, YQ ;
Slee, RB ;
Fukai, N ;
Rawadi, G ;
Roman-Roman, S ;
Reginato, AM ;
Wang, HW ;
Cundy, T ;
Glorieux, FH ;
Lev, D ;
Zacharin, M ;
Oexle, K ;
Marcelino, J ;
Suwairi, W ;
Heeger, S ;
Sabatakos, G ;
Apte, S ;
Adkins, WN ;
Allgrove, J ;
Arslan-Kirchner, M ;
Batch, JA ;
Beighton, P ;
Black, GCM ;
Boles, RG ;
Boon, LM ;
Borrone, C ;
Brunner, HG ;
Carle, GF ;
Dallapiccola, B ;
De Paepe, A ;
Floege, B ;
Halfhide, ML ;
Hall, B ;
Hennekam, RC ;
Hirose, T ;
Jans, A ;
Jüppner, H ;
Kim, CA ;
Keppler-Noreuil, K ;
Kohlschuetter, A ;
LaCombe, D ;
Lambert, M ;
Lemyre, E ;
Letteboer, T ;
Peltonen, L ;
Ramesar, RS ;
Romanengo, M ;
Somer, H ;
Steichen-Gersdorf, E ;
Steinmann, B .
CELL, 2001, 107 (04) :513-523
[10]   LRP5 and Wnt signaling: A union made for bone [J].
Johnson, ML ;
Harnish, K ;
Nusse, R ;
Van Hul, W .
JOURNAL OF BONE AND MINERAL RESEARCH, 2004, 19 (11) :1749-1757