Primary cilia act as gravity transducers in bone cells

Undergraduate Honors Thesis

Citations

Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/8910jv11f

Abstract

Environmental mechanical signals play important roles in the cell fate determination of metazoans, including bone tissues, which utilize mechanical stress to balance the amount of bone formation versus bone resorption. In this case, the force due to gravity is essentially a constant mechanical signal on Earth and has been a key factor in the evolution of skeletal systems in vertebrates. Accordingly, changes in this force, such as is experienced under hyperor microgravity conditions, leads to various cellular responses including altered proliferation, migration, and differentiation. Although the modes of response in vertebrate cells to changes in gravitational acceleration have been widely studied, little is known about how cells initially perceive and transduce these mechanical cues into cellular responses. Previous studies suggest an involvement of primary cilia, non-motile sensory antennae in mammalian cells, which may act as gravity transducers due to their mechanosensory characteristics. However, direct experimental evidence supporting this idea has not yet been established. In my study, I show that primary cilia in bone cells play a role in the mechanotransduction of hypergravity acceleration that influences the regulation of cell proliferation. I also demonstrate that this transduction through primary cilia involves a downstream regulation of global β-catenin levels, particularly at cell-cell contact regions, as well as a loss in the contact inhibition of cell growth.

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