1. Chondrocyte β-Catenin Signaling Regulates Postnatal Bone Remodeling Through Modulation of Osteoclast Formation in a Murine Model.
- Author
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Wang, Baoli, Jin, Hongting, Zhu, Mei, Li, Jia, Zhao, Lan, Zhang, Yejia, Tang, Dezhi, Xiao, Guozhi, Xing, Lianping, Boyce, Brendan F., and Chen, Di
- Subjects
CARTILAGE cells ,TOMOGRAPHY ,ACADEMIC medical centers ,BONE remodeling ,ANIMAL experimentation ,CELLULAR signal transduction ,ENZYME-linked immunosorbent assay ,IMMUNOHISTOCHEMISTRY ,MICE ,POLYMERASE chain reaction ,RESEARCH funding ,WESTERN immunoblotting ,PHYSIOLOGY - Abstract
Objective To investigate whether β-catenin signaling in chondrocytes regulates osteoclastogenesis, thereby contributing to postnatal bone growth and bone remodeling. Methods Mice with conditional knockout (cKO) or conditional activation (cAct) of chondrocyte-specific β- catenin were generated. Changes in bone mass, osteoclast numbers, and osteoblast activity were examined. The mechanisms by which β-catenin signaling in chondrocytes regulates osteoclast formation were determined. Results The β- catenin cKO mice developed localized bone loss, whereas cAct mice developed a high bone mass phenotype. Histologic findings suggested that these phenotypes were caused primarily by impaired osteoclast formation, rather than impaired bone formation. Further molecular signaling analyses revealed that β-catenin signaling controlled this process by regulating the expression of the RANKL and osteoprotegerin (OPG) genes in chondrocytes. Activation of β-catenin signaling in chondrocytes suppressed Rankl gene transcription through a glucocorticoid receptor-dependent mechanism. The severe bone loss phenotype observed in β- catenin cKO mice was largely restored by treatment with human recombinant OPG or transgenic overexpression of Opg in chondrocytes. Conclusion β-catenin signaling in chondrocytes plays a key role in postnatal bone growth and bone remodeling through its regulation of osteoclast formation. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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