Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

被引：31

作者：

Bao, Quanwei ^{[1
]}

Chen, Sixu ^{[1
]}

Qin, Hao ^{[1
]}

Feng, Jianquan ^{[2
]}

Liu, Huayu ^{[1
]}

Liu, Daocheng ^{[1
]}

Li, Ang ^{[1
]}

Shen, Yue ^{[1
]}

Zhong, Xiaozheng ^{[1
]}

Li, Junfeng ^{[1
]}

Zong, Zhaowen ^{[1
]}

机构：

[1] Third Mil Med Univ, Daping Hosp, Dept Trauma Surg, State Key Lab Trauma Burn & Combined Injury, Chongqing 400042, Peoples R China

[2] Baylor Coll Dent, Texas A&M Hlth Sci Ctr, Dept Biomed Sci, Dallas, TX 75246 USA

来源：

EXPERIMENTAL CELL RESEARCH | 2017年 / 350卷 / 01期

基金：

美国国家科学基金会;

关键词：

Wnt/beta-catenin; Constitutive activation of beta-catenin; Osteoblasts; Terminal differentiation; Bone quanlity; DOWN-REGULATION; WNT; PROLIFERATION; SUPPRESSION; EXPRESSION; OSTEOCYTES; RESORPTION; STRENGTH;

D O I：

10.1016/j.yexcr.2016.11.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Accumulating evidence suggests that Wnt/beta-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of eta-catenin (CA-beta-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-beta-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-beta-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-beta-catenin mice. Then the effect of CA-beta-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-beta-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-beta-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-beta-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin Dl, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-beta-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-beta-catenin mice. In summary, osteoblastic CA-beta-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength.

引用

页码：123 / 131

页数：9

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