Cartilage extracellular matrix (ECM), which is secreted by cartilage cells (or chondrocytes), is a highly-organised gel-like substance, where proteoglycan and non-collagenous proteins bind to the collagen, and form a mesh, with water attracted to this mesh by the negatively charged proteins. Together, these components give the matrix its consistency, which in turn, give the tissue its form and function. The ratio of cells to ECM, and the type and proportion of the different ECM components give specific functional properties to the resulting tissue, making it the most appropriate type of cartilage at a given location in the body. Cartilage (joint) defects are often associated with chronic musculoskeletal conditions and affect approximately a third of the population. Such defects are generally replaced by artificial constructs, in the form of a solid plate directly implanted in the joint. However, replacement surgeries are required every 10-15 years, as there is no long-term solution to date for replacing nor regenerating this type of cartilage with properties that are similar to the initial tissue.
We know that cartilaginous fish (sharks and their relatives) have evolved a unique skeletal system made of cartilage. Interestingly, the capacity of their skeleton to withstand higher pressures, at depths, has not been explored yet. These animals can cope with continuous high hydrostatic pressures, from 10 to 1,000 times greater than sea level, depending on the depth zone they live in. While similar conditions can cause overwhelming mechanical stress leading to acute tissue damage in terrestrial mammals, cellular mechanisms, structural organisation, and composition of their ECM must have evolved to persistently protect their skeletal tissues.
We therefore hypothesise that the cartilage tissues of deep-sea fish are different from mammalian cartilage types, and are adapted to the high-pressure environment they live in. Specifically, we predict that the ECM will show differences in microstructure, composition, and mechanical properties, and that there will be site-specific differences in the levels of mineralisation, cellular physiology and biophysical properties, in order to maintain tissue integrity under such pressures. Understanding natural adaptations of cartilage in extreme environments and load cases is of critical importance to explore future potential applications in cartilage tissue engineering and regenerative medicine, such as the development of novel methods to produce damage-resistant bioengineered constructs that better treat cartilage defects in humans.
Our team aims to unravel key biomechanical adaptations in the cartilage tissues of these lesser-known fish, looking at several skeletal areas of interest across selected species. This “fish cartilage” project interfaces with the “Human ECM” and “Network Architecture” projects of the MPQC, resulting in new insights on the role of multiscale tissue architecture on transport properties of ECMs.
Acknowledgement – this project was made possible by the cooperation and assistance in the specimen collection provided by the staff and crew of the RV Tangaroa, and Dr. Brittany Finucci at the National Institute of Water and Atmospheric Research (NIWA), New Zealand.