The most prevalent form of degeneration of cartilage joint is osteoarthritis (OA), currently affecting 5.2 million people in the UK. OA is highly widespread within the aging population, which is why has been suggested to correlate with ageing. This chronic disease promotes the irreversible breakdown of the tissue with abnormal remodelling resulting in a mechanical fault and leading to increased brittleness and stiffness as a consequence of the reduction in proteoglycan content and the increase of collagen crosslinks. Due to the limited repair capacity of the articular cartilage the therapeutic efforts for prevention and repair of cartilage injury currently focus on developing repairing techniques, such as cell therapy of autologous chondrocytes implantation. Attempts to repair the complex morphology of cartilage are still a challenge due to its complexity and the diverse composition within each region.

From http://www.bouncepodiatry.com.au

Here‘s a great video by Versus Arthritis explaining osteoarthritis

Cartilage ageing is a complex process involving the death of cells, ECM remodelling and matrix modifications independent of cells, such as collagen cross-linking or accumulation of age related glycation end products. The processes of cell death and matrix remodelling are currently investigated by several teams, recent studies suggesting that the cell death and survival are highly related to the ECM integrity. Moreover, several studies suggested a relation in the failure of responding to the mechanical forces in chondrocytes with no functional and modified primary cilia presented in OA patients. In healthy chondrocytes cilia presented mechanotransducers molecules such as integrin, and seemed to have a role as sensory organelle in mechanotransduction for signalling pathways. However, the influence the ageing on the matrix may have on the cell signalling and the cellular phenotype remains to be elucidated. Consequently, understanding of the ageing and OA degenerative process are key to clarify how the cell death and ECM modifications are implicated in the degradation of the biomechanical properties. We are currently trying to address this through a project kindly funded by the NC3Rs.

Several skeletal dysplasias present with osteoarthritis as an additional complication, either due to associated joint laxity and instability or cartilage structural brittleness. OA in the general population is a difficult disease to study due to its multifactorial aspect. It can be affected by genetic susceptibility as well as age, lifestyle, injuries and many other factors.  Studying its progression in the monogenic conditions such as skeletal dysplasias is an added advantage and allows us to find the common mechanisms amonst the rare. The SYBIL project that we were involved in in 2013-2018 was focused on dissecting these disease mechanisms in detail.

More recently, through a collaboration with Lund University in Sweden, we have found that asporin, a small leucine rich proteoglycan, may in fact be chondroprotective in OA. Asporin is found in perichondrium, periosteum and periodontal ligaments. It is not present in healthy cartilage; however, it is expressed in the OA cartilage, indicating it might play a role in the disease progression. Moreover, a polymorphism in ASPN gene has been linked to OA susceptibility and shown to suppress TGFβ-mediated expression of extracellular matrix (ECM) genes in OA cartilage. However, the role of asporin in the context of healthy musculoskeletal ageing and OA progression has not been investigated in detail. We currently have two projects investigating the role of asporin in musculoskeletal development and health, a PhD project funded by JGW Patterson Foundation using mesenchymal stem cells and siRNA and CRISPR/Cas9 technology to delete asporin in musculoskeletal development, and a Dunhill Medical Trust funded research project utilising mouse models to study the role of asporin in OA progression. The results of both these studies will be shared through this website. If you would like to know more, please do not hesitate to contact us.