title: Roles of Wnt/β-catenin signalling pathway in the bony repair of injured growth plate cartilage in young rats.
abstract: Growth plate cartilage is responsible for longitudinal growth of the long bone in children, and its injury is often repaired by bony tissue, which can cause limb length discrepancy and/or bone angulation deformities. Whilst earlier studies with a rat growth plate injury repair model have identified inflammatory, mesenchymal infiltration, osteogenesis and remodeling responses, the molecular mechanisms involved in the bony repair remain unknown. Since our recent microarray study has strongly suggested involvement of Wnt-β-catenin signalling pathway in regulating the growth plate repair and the pathway is known to play a crucial role in the osteogenic differentiation of mesenchymal progenitor cells, the current study investigated the potential roles of Wnt-β-catenin signalling pathway in the bony repair of injured tibial growth plate in rats. Immunohistochemical analysis of the growth plate injury site revealed β-catenin immunopositive cells within the growth plate injury site. Treatment of the injured rats with the β-catenin inhibitor ICG-001 (oral gavage at 200mg/kg/day for 8days, commenced at day 2 post injury) enhanced COL2A1 gene expression (by qRT-PCR) and increased proportion of cartilage tissue (by histological analysis), but decreased level of osterix expression and amount of bone tissue, at the injury site by day 10 post-injury (n=8, P<0.01 compared to vehicle controls). Consistently, in vitro studies with bone marrow stromal cells from normal rats showed that β-catenin inhibitor ICG-001 dose dependently inhibited expression of Wnt target genes Cyclin D1 and survivin (P<0.01). At 25mM, ICG-001 suppressed osteogenic (by CFU-f-ALP assay) but enhanced chondrogenic (by pellet culture) differentiation. These results suggest that Wnt/β-catenin signalling pathway is involved in regulating growth plate injury repair by promoting osteoblastogenesis, and that intervention of this signalling could represent a potential approach in enhancing cartilage repair after growth plate injury.
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. rosa.chung@unisa.edu.au
authors.forename: Rosa
authors.initials: R
authors.lastname: Chung
authors.forename: Derick
authors.initials: D
authors.lastname: Wong
authors.forename: Carmen
authors.initials: C
authors.lastname: Macsai
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piergentili
authors.forename: Fabio
authors.initials: F
authors.lastname: Del Bello
authors.forename: Wilma
authors.initials: W
authors.lastname: Quaglia
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072042:Salter-Harris Fractures; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C492448:ICG 001; D011744:Pyrimidinones; D051176:beta Catenin