Íris Halldórsdóttir, Sara Sigurbjörnsdóttir and Abbi Smith
Introduction: Osteoarthritis is a musculoskeletal disorder that affects millions of people worldwide. Chondrocytes, which are the only resident cells of articular cartilage, can change to a hypertrophic phenotype in osteoarthritic cartilage. The hedgehog signalling pathway is important in development and tissue homeostasis, and abnormal activation of this pathway has also been linked with osteoarthritis. Zebrafish (Danio rerio) serve as a valuable model for studying musculoskeletal disorders, sharing over 80% of known disease-causing genes with humans and exhibiting bone development that closely mirrors our own. We generated a transgenic zebrafish line with fluorescently labelled chondrocytes to track the phenotype of chondrocyte cells over time in response to changes in hedgehog signalling.
Methods: We generated a construct that included a chondrocyte-specific type II collagen reporter and GFP, which will integrate into the zebrafish genome with the Tol2 transposon system. This construct was then microinjected into zebrafish embryos and the fluorescent signal assessed. The effects of hedgehog signalling on chondrocyte morphology was investigated using drug treatments to either activate or inhibit hedgehog signalling.
Results: Injecting our construct into zebrafish larvae has yielded fluorescently positive chondrocytes in zebrafish embryos. When hedgehog signalling was modified in zebrafish larvae with fluorescently labelled chondrocytes, we observed a difference in the chondrocyte phenotype and developing bone morphology.
Conclusions: Hedgehog signalling is important during development, and dysregulation has been associated with osteoarthritis. Altering hedgehog signalling in zebrafish larvae disrupts normal jaw formation. This supports the hypothesis that hedgehog signalling is important in cartilage development in zebrafish.
