Large Animal Surgery Resident Oregon State University Corvallis , Oregon
Localized Gene Expression of Hedgehog and Growth Factor Signaling at the Cartilage Canals and Osteochondral Junction in Equine Osteochondrosis. Marchant L, Semevolos S, Duesterdieck-Zellmer K. Oregon State University, Carlson College of Veterinary Medicine, Department of Clinical Sciences, Corvallis, OR.
Osteochondrosis (OC) is a developmental orthopedic disease that results from a disruption to normal endochondral ossification in the articular-epiphyseal growth complex. Cellular pathways regulating this process include hedgehog and growth factor signaling. This study compared gene expression between OC affected and normal cartilage at specific locations in the articular cartilage. We hypothesized that OC samples would have upregulated gene expression of hedgehog signaling and growth factors, with downregulation of hedgehog transcription factor Gli1. Archived femoropatellar samples from foals aged 1–6 months were utilized and chondrocytes from the cartilage canal and osteochondral junction were obtained using laser capture microdissection. Quantitative real-time PCR was performed on nine target genes, including Gli1, Gli3, Patched1, Patched2, Smoothened, PTHrP-Receptor1, TGF- β, IGF-Iα, and PDGF- β. OC and normal samples were compared with the Mann-Whitney U test (P ≤ 0.05). There was significantly lower gene expression of Gli1 (P = 0.016) in chondrocytes surrounding cartilage canals of OC samples versus controls. In OC samples, IGF-I α expression was significantly higher near cartilage canals (P = 0.0317) compared to controls. The remainder of the genes showed no significant difference at either location. This work demonstrated differential gene expression of hedgehog signaling and growth factors in chondrocytes at the cartilage canals. Limitations of the study include difficulty correlating gene to protein expression and lack of direct cause and effect. These results could reflect a loss of hedgehog signaling with concurrent chondrocyte repair near the cartilage canals. The results of this study contribute to the understanding of the pathogenesis of osteochondrosis.