Systems mechanobiology in intervertebral disc degeneration and osteoarthritis

While the burden of infectious diseases has decreased over the last decades globally, the one of Non-Communicable Disease and Disorders (NCD) continues increasing, in terms of premature loss of life quality and years of life. As such, NCD represents 70% of the top-10 disabling and life threatening diseases and disorders worldwide. Remarkably, more than half of these NCD affects mechanical load-bearing organs and tissues, and the identification of modifiable risk factors and of therapeutic targets is a major challenge. On the one hand, NCD can evolve subclinically over decades. On the other hand, the mechanoregulation of the cells that populate and regulate load-bearing tissues and organs makes pathophysiological processes be hugely multifactorial, driven by intricate physical, biophysical and biological phenomena. Computer models and simulations able to mechanistically represent key regulation phenomena over the scales are becoming increasingly valuable, to identify different pathophysiological mechanisms and stratify risk factors, for example in musculoskeletal joint degeneration. Yet, a large spectrum of the computer models and simulations must be employed, combining physics-based, biologybased, systems-based, and knowledge- and data-driven modelling. An overview of the development, analysis and achievements of such heterogeneous modelling approach, in rheumatology, will be given.