Skip to main content

An interdisciplinary approach to uncover the mechanisms of progression of cartilage damage at the cellular and tissue levels

Periodic Reporting for period 1 - INpaCT (An interdisciplinary approach to uncover the mechanisms of progression of cartilage damage at the cellular and tissue levels)

Reporting period: 2017-01-01 to 2018-12-31

Osteoarthritis (OA) affects millions of people and is the most common cause of pain and physical disability in the world today, with huge social and economic costs. In Europe, over 40 million people are affected by OA. It is estimated that 130 million Europeans will suffer from OA by 2050. An estimated 52.5 million of people in the US suffer from OA and the total costs exceed $100 billion per year. Although age is a major risk factor for OA, joint injury also contributes to acute and long-term cartilage degradation in younger population.
Presently, there is no treatment that can reverse or halt OA, other than pain-relief until joint replacement becomes necessary. Abnormal mechanical loading plays an important role in the progression of cartilage degeneration after injury. Since injured cartilage has limited intrinsic repair capacity, a thorough understanding of mechanobiological mechanisms at cellular and tissue levels in normal and pathological conditions is essential for developing effective treatments to restore function and prevent disease progression.
INpaCT focuses on elucidating key players involved in the progression of cartilage damage following injury using sophisticated microscopic, spectroscopic and molecular biology techniques combined with computational modelling and optimization algorithms. This will provide novel insights into disease mechanisms and ultimately improved repair strategies. The overall goal of INpaCT is to explore the underlying mechanisms at cellular and tissue level in a controlled in vitro model of osteoarthritis progression. We aim to determine poro-viscoelastic properties of healthy/damaged cells and their pericellular matrix in an intro model of osteoarthritis progression using a novel approach coupling Atomic Force Microscopy (AFM) measurements, computational modelling and optimization algorithms. In addition, changes in cartilage structure, composition and metabolism in an in vitro model of osteoarthritis progression will be investigated.
Cartilage explants from the in vitro model of OA progression were collected at different time points and changes in the structure (proteoglycan content PG) and cell viability were assessed. The experimental results demonstrated a reduction in PG content around the defect and a decrease in cell viability at 12 days after injury followed by dynamic compression. We developed and validated a cartilage degeneration algorithm based on these experimental findings. Two driving mechanisms, fluid flow and tissue deformation were identified as responsible for the cell death and tissue degradation observed experimentally when a normal dynamic loading was applied to the explant. The results of this study were published in Scientific Reports. Currently, we are investigating the effects and interrelationships of cartilage inflammation and injury at different cartilage length scales. The reported work was performed at Massachusetts Institute of Technology (MIT) and will be continued at University of Eastern Finland (UEF).
In the first two years of the project, essential steps have been taken to identify the key players involved in the progression of cartilage degeneration following injury using an interdisciplinary approach combining material testing, computational modelling and sophisticated microscopic, microspectroscopic and molecular biology techniques. Understanding the underlying mechanisms of progression of cartilage damage after injury will have an impact on development of future novel strategies for prevention, rehabilitation, repair and/replacement.
This project increases the competitiveness of musculoskeletal research area in Europe by embedding new research knowledge and state-of-the-art techniques acquired by the fellow from MIT within the host lab in Finland. This project also established a long-term collaboration between MIT and UEF and opened new opportunities for joint research projects and joint supervision between the two universities.
INpaCT project overview