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The role of the meniscus in the development of knee osteoarthritis - A research project funded by the European Research Council

Picture of Professor Martin Englund, the background is blurry green.

The European Research Council (ERC) is a key research funder in Europe funding researchers with projects with potential to be ground-breaking across all fields of science. As the principal investigator for a project, Professor Martin Englund at Lund University, has been fortunate to have had such funding for a 5-year period for a project in the field of osteoarthritis.

The menisci in the knee are two wedge shaped cartilage pieces that provide load distribution and stability within the knee joint. His prior research leading up to the ERC project was based on findings that torn menisci are common in the general population of middle-aged and elderly. Such meniscal lesions (due to loss of meniscus function) are also risk factors for the development of knee osteoarthritis. Most of these lesions seem to be a result of slow degenerative processes and not by acute knee trauma. Thus, the overarching aim of the project was to gain new insights into the molecular components of meniscus tissue in the different stages of osteoarthritis development. Such knowledge would help us in the future in identifying new therapeutic strategies to tackle this common disease, causing pain, aching, reduced function and disability.

Martin, his team and scientific close collaborators have published a number of scientific papers as a result of the project (please see list below), and more exciting work is ongoing. Here are some of the key findings as of yet:

The team has demonstrated the vastly changed micro-structure of the meniscus in late-stage osteoarthritis using an advanced imaging technique of tissue samples called micro-tomography. This technique visually demonstrates that osteoarthritis is severely affecting the meniscal tissue as well and not only the joint cartilage of the knee.(Ref 2019, Kestilä et al. Three-dimensional microstructure of human meniscus posterior horn in health and osteoarthritis)

Using another advanced experimental imaging technique based on magnetic resonance imaging (MRI), the team determined the different appearance of the meniscal tissue from different stages of osteoarthritis development. Thus, the technique has potential for future diagnostic purposes in the early stages of disease, but also to monitor effects of different novel osteoarthritis treatment candidates. (Ref 2020, Einarsson et al. Relating MR relaxation times of ex vivo meniscus to tissue degeneration through comparison with histopathology) 

MRI images of meniscus sample with and without osteoarthritis.
Example MRI images and corresponding map from the relaxation parameter T2* of meniscus samples from knees with (right) and without (left) known knee osteoarthritis. Picture: Emma Einarsson

The team’s molecular analyses of both healthy menisci and menisci from osteoarthritis patients show that the inner meniscus is typically affected in support of strong biomechanical contribution to disease development, as most knee osteoarthritis is located to the inner side of the knee. (Ref 2020, Folkesson et al. Proteomic comparison of osteoarthritic and reference human menisci using data-independent acquisition mass spectrometry.)

Also, the team’s analyses of the fluid within the knee joint, so called synovial fluid, indicates a profound disruption of the interplay between the proteins already in the earlier stages of osteoarthritis in support of multiple opportunities for interventions that can prevent, slow, halt or reverse the pathologic processes.(Ref 2022, Ali Proteomics profiling of human synovial fluid suggests increased protein interplay in early-osteoarthritis (OA) that is lost in late-stage OA. Ref 2023, Rydén. Identification and quantification of degradome components in human synovial fluid reveals an increased proteolytic activity in knee osteoarthritis patients vs controls)

The work of Martin’s team to gain new insights into the pathologic processes of joint cartilage and meniscus in osteoarthritis continues. For instance, they are developing experimental models in the laboratory where they plan to simulate what joint tissue may be exposed to in everyday life. Different scenarios may include if having torn menisci or if being overweight or obese, and the team will measure in detail the cells’ molecular responses to loading to elucidate the role of physical activity, where “too little” or “too much” may both be detrimental, and give clues to potential new therapeutic options.

Learn more about ERC on their webpage, link will open in a new tab.