title: Chondrocyte β-catenin signaling regulates postnatal bone remodeling through modulation of osteoclast formation in a murine model.
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.
  
  
  CONCLUSIONS
  β-catenin signaling in chondrocytes plays a key role in postnatal bone growth and bone remodeling through its regulation of osteoclast formation.
authors.affiliation: University of Rochester, Rochester, New York; Metabolic Diseases Hospital and Tianjin Medical University, Tianjin, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Wang
authors.forename: Hongting
authors.initials: H
authors.lastname: Jin
authors.forename: Mei
authors.initials: M
authors.lastname: Zhu
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Zhao
authors.forename: Yejia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dezhi
authors.initials: D
authors.lastname: Tang
authors.forename: Guozhi
authors.initials: G
authors.lastname: Xiao
authors.forename: Lianping
authors.initials: L
authors.lastname: Xing
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Boyce
authors.forename: Di
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D016723:Bone Remodeling / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019902:Chondrocytes / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D051176:beta Catenin