Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice
Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteo...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2018-08-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/492549 |
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| author | Xin Sui Shijian Deng Mengmeng Liu Linlin Fan Yunfei Wang Huaxing Xu Yao Sun Anil Kishen Qi Zhang |
| author_facet | Xin Sui Shijian Deng Mengmeng Liu Linlin Fan Yunfei Wang Huaxing Xu Yao Sun Anil Kishen Qi Zhang |
| author_sort | Xin Sui |
| collection | DOAJ |
| description | Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+, designated CA-β-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss. |
| first_indexed | 2024-12-10T22:06:09Z |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-10T22:06:09Z |
| publishDate | 2018-08-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-c086ab50bc4e43e39cb73f17ee0454a42022-12-22T01:31:44ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-08-014852091210210.1159/000492549492549Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in MiceXin SuiShijian DengMengmeng LiuLinlin FanYunfei WangHuaxing XuYao SunAnil KishenQi ZhangBackground/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+, designated CA-β-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss.https://www.karger.com/Article/FullText/492549Β-cateninWnt/β-catenin signalling pathwayOsteoclastOsteoclastogenesisBone homeostasis |
| spellingShingle | Xin Sui Shijian Deng Mengmeng Liu Linlin Fan Yunfei Wang Huaxing Xu Yao Sun Anil Kishen Qi Zhang Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice Cellular Physiology and Biochemistry Β-catenin Wnt/β-catenin signalling pathway Osteoclast Osteoclastogenesis Bone homeostasis |
| title | Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice |
| title_full | Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice |
| title_fullStr | Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice |
| title_full_unstemmed | Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice |
| title_short | Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice |
| title_sort | constitutive activation of β catenin in differentiated osteoclasts induces bone loss in mice |
| topic | Β-catenin Wnt/β-catenin signalling pathway Osteoclast Osteoclastogenesis Bone homeostasis |
| url | https://www.karger.com/Article/FullText/492549 |
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