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Brother of CDO (BOC) expression in equine articular cartilage
K S Vanderman1, M Tremblay, W Zhu
1Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Abstract:
Brother of CDO (BOC) is a cell surface receptor that derives its name from the structurally related protein, cell adhesion molecule-related/down-regulated by oncogenes (CDO, sometimes CDON). High levels of BOC mRNA and protein expression have been described in embryonic tissues with active cell proliferation and ongoing cellular differentiation(1,2). A microarray-based screen of RNA isolated from 11 different adult equine tissues unexpectedly identified BOC as having an expression pattern restricted to articular cartilage. The objective of this study was to further investigate BOC expression in adult articular cartilage relative to other tissues. Both RT-qPCR and mRNA sequencing confirmed the microarray data. Steady state BOC mRNA levels in articular cartilage were substantially higher than in the other adult tissues tested, neonatal tendon, placenta, and whole embryo. The expression of BOC displayed a pattern of tissue specificity comparable to well established cartilage matrix protein biomarkers. BOC mRNA levels in articular cartilage increased with age, but were rapidly down-regulated when chondrocytes were enzymatically isolated from the cartilage matrix and expanded in monolayer culture. Relative expression patterns of CDO were broadly similar, but displayed lower fold change differences. A functional role in articular cartilage that involves Hedgehog signaling is suggested by the known binding affinity of BOC for all three Hedgehog ligands. These data also extend BOC and CDO biology to a post-mitotic and highly differentiated cell type within a mature tissue.
Insights
Brother of CDO (BOC) is highly expressed in adult articular cartilage, unlike embryonic tissues. BOC levels increase with age but decrease when chondrocytes are cultured, suggesting a role in cartilage biology and Hedgehog signaling.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Brother of CDO (BOC) is a cell surface receptor related to cell adhesion molecule-related/down-regulated by oncogenes (CDO).
- BOC is typically found in embryonic tissues with high cell proliferation and differentiation.
Purpose of the Study:
- To investigate BOC expression in adult equine articular cartilage compared to other tissues.
- To understand BOC's role in differentiated chondrocytes and its relationship with Hedgehog signaling.
Main Methods:
- Microarray analysis of 11 adult equine tissues.
- Quantitative reverse transcription PCR (RT-qPCR) and mRNA sequencing.
- Analysis of BOC expression in cultured chondrocytes and correlation with age.
Main Results:
- BOC mRNA expression was unexpectedly restricted to adult articular cartilage, exceeding levels in other tested tissues.
- BOC expression in articular cartilage increased with age but decreased upon chondrocyte isolation and culture.
- CDO expression patterns were similar but less pronounced; BOC's affinity for Hedgehog ligands suggests a functional role.
Conclusions:
- BOC is a tissue-specific marker for adult articular cartilage with age-dependent regulation.
- BOC and CDO play roles in differentiated chondrocytes, potentially through Hedgehog signaling pathways.
- This study expands the known biology of BOC and CDO to mature, post-mitotic cells.
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