Exposure to hypergravity during zebrafish development alters cartilage material properties and strain distribution

Abstract

Aims Vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, with sarcopenia and osteoporosis observed in astronauts returning from space, the effects of shorter exposures to increased gravitational fields are less well characterized. We aimed to test how hypergravity affects early cartilage and skeletal development in a zebrafish model. Methods We exposed zebrafish to 3 g and 6 g hypergravity from three to five days post-fertilization, when key events in jaw cartilage morphogenesis occur. Following this exposure, we performed immunostaining along with a range of histological stains and transmission electron microscopy (TEM) to examine cartilage morphology and structure, atomic force microscopy (AFM) and nanoindentation experiments to investigate the cartilage material properties, and finite element modelling to map the pattern of strain and stress in the skeletal rudiments. Results We did not observe changes to larval growth, or morphology of cartilage or muscle. However, we observed altered mechanical properties of jaw cartilages, and in these regions we saw changes to chondrocyte morphology and extracellular matrix (ECM) composition. These areas also correspond to places where strain and stress distribution are predicted to be most different following hypergravity exposure. Conclusion Our results suggest that altered mechanical loading, through hypergravity exposure, affects chondrocyte maturation and ECM components, ultimately leading to changes to cartilage structure and function. Cite this article: Bone Joint Res 2021;10(2):137–148.