title: Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality.
abstract: Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-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-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-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-β-catenin mice. Then the effect of CA-β-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-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-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-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength.
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Quanwei
authors.initials: Q
authors.lastname: Bao
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Sixu
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, TX 75246, USA.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Daocheng
authors.initials: D
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Xiaozheng
authors.initials: X
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042, China. Electronic address: zongzhaowen@sina.cn.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zong
mesh_terms: D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Bone quanlity; Constitutive activation of β-catenin; Osteoblasts; Terminal differentiation; Wnt/β-catenin