Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023

Designing the zebrafish model organism for musculoskeletal disease toolkit

Höfundar / Authors: Abbi Smith, Íris Halldórsdóttir, Eiríkur Steingrímsson, Sara Sigurbjörnsdóttir

Starfsvettvangur / Affiliations: 1. Faculty of Medicine, School of Health Sciences, University of Iceland 2. Faculty of Life and Environmental Science, School of Engineering and Natural Sciences, University of Iceland 3. Faculty of Medicine, School of Health Sciences, University of Iceland 4. Faculty of Life and Environmental Science, School of Engineering and Natural Sciences, University of Iceland

Kynnir / Presenter: Abbi Elise Smith

Osteoarthritis is a debilitating, degenerative joint disease with no known cure. It is characterized by the destruction of healthy articular cartilage leading to pain and inflammation that not only affects the cartilage, but also the synovium and subchondral bone. Hedgehog signaling is critical for normal musculoskeletal development and is also known to be increased in osteoarthritic articular cartilage compared to healthy cartilage. A mutation of the gene Smoothened identified in a large-scale GWAS is predicted to decrease or abolish the binding of cholesterol thereby inhibiting downstream hedgehog signaling. Interestingly, this mutation also has a high association with the development of hip osteoarthritis, contradicting the classic hedgehog signaling and osteoarthritis paradigm. Our lab seeks to investigate further the role of hedgehog signaling in osteoarthritis, the effect of cholesterol-binding mutations of Smoothened in osteoarthritis, and to build a toolbox of in vitro and in vivo technologies and techniques to study osteoarthritis and other diseases. We are utilizing zebrafish (Danio rerio) to investigate the effects of cholesterol binding mutations of Smoothened on downstream hedgehog signaling and cartilage and bone development using a variety of techniques that include mRNA microinjection of zebrafish embryos, qPCR, morphological assessments, micro-CT and more.