Growth plate cartilage is responsible for bone lengthening in children, and its injury is often repaired by bony tissue, which can cause limb length discrepancy and/or bone angulation deformities. While earlier studies on growth plate injury repair have identified inflammatory, mesenchymal infiltration, osteogenesis and remodelling repair responses, the molecular mechanisms involved in the bony repair remain unknown. Since the Wnt-β-catenin signalling pathway is known to play a crucial role in the osteogenic differentiation of mesenchymal progenitor cells, this study investigated the potential roles of Wnt-β-catenin signalling pathway in the bony repair of injured growth plate in rats. Suggestive of a role of Wnt/β-catenin signalling pathway in the early stage of the repair, our Affymetrix gene microarray analysis with RNA isolated from laser-capture microdissected injury site tissue identified an increase in β-catenin expression and yet a decrease in expression of Wnt signalling inhibitors sFRP1 & 4 at day 4 post-injury vs later time points. Compared to the vehicle control, treatment of the injured rats with the β-catenin inhibitor ICG-001 (oral gavage at 200 mg/kg/day for 8 days, commenced at day 2 post injury) enhanced collagen-2 gene expression (by qRT-PCR), increased proportion of cartilage tissue and decreased level of bone tissue (as measured by histological analysis) at the injury site by day 10 postinjury (n=8, p<0.001). Consistently, in vitro studies with bone marrow stromal cells from normal rats showed that β-catenin inhibitor ICG-001 at 25 mM suppressed osteogenic (by CFU-f-ALP assay) but enhanced chondrogenic (by pellet culture) differentiation. These results suggest that Wnt-β-catenin signalling promotes osteoblast differentiation and suppresses chondrogenic differentiation during bony repair of the injured growth plate, and intervention of this signalling could represent a potential approach in enhancing cartilage regeneration after growth plate injury.
Inhibition of WNT-β-catenin signalling promotes cartilage repair at injured growth plate in young rats
PIERGENTILI, Alessandro;
2012-01-01
Abstract
Growth plate cartilage is responsible for bone lengthening in children, and its injury is often repaired by bony tissue, which can cause limb length discrepancy and/or bone angulation deformities. While earlier studies on growth plate injury repair have identified inflammatory, mesenchymal infiltration, osteogenesis and remodelling repair responses, the molecular mechanisms involved in the bony repair remain unknown. Since the Wnt-β-catenin signalling pathway is known to play a crucial role in the osteogenic differentiation of mesenchymal progenitor cells, this study investigated the potential roles of Wnt-β-catenin signalling pathway in the bony repair of injured growth plate in rats. Suggestive of a role of Wnt/β-catenin signalling pathway in the early stage of the repair, our Affymetrix gene microarray analysis with RNA isolated from laser-capture microdissected injury site tissue identified an increase in β-catenin expression and yet a decrease in expression of Wnt signalling inhibitors sFRP1 & 4 at day 4 post-injury vs later time points. Compared to the vehicle control, treatment of the injured rats with the β-catenin inhibitor ICG-001 (oral gavage at 200 mg/kg/day for 8 days, commenced at day 2 post injury) enhanced collagen-2 gene expression (by qRT-PCR), increased proportion of cartilage tissue and decreased level of bone tissue (as measured by histological analysis) at the injury site by day 10 postinjury (n=8, p<0.001). Consistently, in vitro studies with bone marrow stromal cells from normal rats showed that β-catenin inhibitor ICG-001 at 25 mM suppressed osteogenic (by CFU-f-ALP assay) but enhanced chondrogenic (by pellet culture) differentiation. These results suggest that Wnt-β-catenin signalling promotes osteoblast differentiation and suppresses chondrogenic differentiation during bony repair of the injured growth plate, and intervention of this signalling could represent a potential approach in enhancing cartilage regeneration after growth plate injury.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
