Ciliary signalling and the extracellular matrix
- University of Auckland.
- University of Western Australia.
Nearly all cells in the body have a primary cilium, a specialised compartment perfectly evolved to be a cellular probe. Primary cilia are microtubule-based organelles (1-15μm long, 200nm wide) that are formed from the centriolar anchor known as the basal body. Primary cilia act as cellular sensors that receive diverse signals from the extracellular environment including light, growth factors and mechanical stimuli in a tissue-specific manner. The cilium is also separated for the main cell body through a ciliary gate known as the transition zone. Our work has focussed on ECM/ cilia interactions in connective tissues such as articular cartilage and the intervertebral disc. Structurally, chondrocyte cilia are structurally associated with the collagen fibres, they express integrins and are mechanically deflected through ECM interactions. We, and others, have shown that chondrocyte primary cilia mechanosensitive, whereby cilia incidence and length are modulated by compressive or tensile forces, and removal of cilia results in in reduced mechanotransduction, and alterations in cartilage ECM gene expression. Current research focuses on chemical, specific mechanical forces such as fluid flow, or gene cues that control cilia, however, few studies have examined how the mechanics of the local microenvironment influences cilia function. We have examined how cilia length and incidence is influenced by different ECM environments in diseases such in osteoarthritis, intervertebral disc disease and, more recently in model gel systems with controlled stiffness. Our data suggest an intricate relationship between substrate stiffness, F-actin and cilia length and more work is essential to understand the critical role of the mechanical microenvironment on ciliary signalling.