Wow! What a semester. Having signed up to the MSci during final year, I definitely didn’t predict how the first semester would go. Busy. But enjoyable! However, I think one thing that took everyone in the group by surprise was these blogs. We all started a bit tentatively, but I believe we have enjoyed writing them, and embraced the opportunity to write about science in a format other than an essay! So now we move onto second semester and the project. I am lucky enough to be working with Dr Nalesso, tasked with trying to understand mechanisms behind the onset of osteoarthrosis and here you can read a bit of background information into what I will be doing.
Osteoarthritis (OA) is the most common form of arthritis in the UK. It is a condition which causes joints to become painful, stiff and inflamed and often becomes debilitating. It is a massive problem, to the extent that the majority of individuals over the age of 65 have radiographic or clinical evidence of osteoarthritis, with an estimated 242 million people affected with OA of the hip or knee worldwide (NHS, 2019).
The likelihood is that most of you reading this know more than a few people affected by OA, quite often within the immediate family. If so, you may know that there are currently no treatments on offer for patients with OA, only methods of managing the symptoms. Simple measures, such as losing weight, using knee supports and wearing better-quality shoes can lessen the pain by reducing strain on the joints. In more extreme cases, people may need to take painkillers or undergo surgery, the likes of knee or hip replacements in order to manage their symptoms of OA.
So, what causes OA? Cartilage is connective tissue found within the joints between bones which reduces friction so that the joints can bear and distribute weight, preventing mechanical stress. Interestingly, usually the only cell found within healthy cartilage are the chondrocytes. They maintain the immediate environment around themselves through the production of different compounds such as ‘collagen’ which keep our joints healthy. The figure below shows how joints are affected during OA.
Upon the onset of OA, the chondrocytes undergo something called de-differentiation, which is changes in growth, viability, the chemicals they release, and the cells increase in size. Consequently, they lose their ability to maintain the immediate environment in the synovial fluid shown in the diagram above. Importantly, as the chondrocytes de-differentiate, they also lose the ability to activate a signalling pathway called the Wnt pathway. These changes mean the cells can no longer effectively produce an environment within the joints which allows for minimal friction and appropriate weight distribution, leading to pain and inflammation.
The Wnt pathway is a signal transduction pathway, meaning it amplifies an initial signal into numerous signals, producing a change in the behaviour of cells through altered expression of different proteins. Usually Wnt signalling causes Beta-Catenin (BC) to be created. But at the same time Wnt prevents BC from being broken down, which means BC builds up within cells over time. It has been hypothesised that the loss of the function as chondrocytes de-differentiate may be important in the onset of OA. However, the associated reasons as to why/how the signalling affects the chondrocytes is still unknown.
Now you know the background behind my project we can talk about the aims. We aim to conduct some research which will hopefully further our understanding in the Wnt pathway and how it affects the de-differentiation of articular chondrocytes, hopefully resulting in revealing a potential drug target. A new drug target represents potential, and potential for scientific treatments is always exciting!
Charlier E, Deroyer C, Ciregia F, Malaise O, Neuville S, Plener Z, Malaise M, de Seny D (2019) Chondrocyte dedifferentiation and osteoarthritis (OA), Biochemical Pharmacology pp. 49-65.
Huelsken J, Behrens J (2002) The Wnt signalling pathway, Journal of Cell Science, 115.
Mandal A, Robertson S (2019) What is Cartilage?, News Medical Life Science, Available at: https://www.news-medical.net/health/What-is-Cartilage.aspx [Accessed: 12-Nov-2019].
NHS (2019) Osteoarthritis Overview, NHS, Available at: https://www.nhs.uk/conditions/osteoarthritis/ [Accessed: 12-Nov-2019].