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Department of Musculoskeletal and Ageing Science, University of Liverpool
Liverpool, UK
Closing date: Fri 10 May 2024
We are seeking a motivated individual to work on this exciting project investigating the role that the calcified cartilage has in rare and common joint osteoarthritis, using novel approaches such as gene silencing and establishment of a 3D chondrocyte cell culture model.
OA, a world-wide healthcare burden, has no effective disease modifying treatment available. There is a need to understand the mechanism(s) by which cartilage destruction occurs in OA to pinpoint new therapeutic targets. Studying human OA is difficult and limited to imaging modalities and donated tissue with end-stage disease in which it is too late to unravel a mechanism. Researching rare forms of OA however can uncover disease mechanisms amplified or accelerated by genetic defects. Trabecular excrescences and high-density mineralised protrusions are example of osteoarthritic features first identified in the rare disease alkaptonuria (AKU). AKU is a degenerative disorder characterised by tissue pigmentation (ochronosis) leading to severe and early onset OA. In AKU, homogentisic acid (HGA) is not metabolised by the liver and enters the circulation, and overtime causes pigmentation of connective tissues, particularly cartilage.
By studying AKU, this project aims to understand the pathophysiological changes that articular cartilage undergoes with natural ageing that firstly allows pigment to bind, and secondly how this pigmentation leads to severe OA. This project will use murine models of OA such as STR/Ort in collaboration with Prof Pitsillides lab, and AKU mice known as Hgd-/- generated by us here in Liverpool, alongside in vitro work. The calcified cartilage, which is very understudied, is an area of focus in this project, as both AKU and STR/Ort mice both show early pathological changes, such as pigmentation and hypertrophy respectively, before changes in non-calcified articular cartilage are observed.
Read more details at: https://www.findaphd.com/phds/project/study-of-early-pathological-changes-in-calcified-cartilage-in-osteoarthritis-and-alkaptonuria/?p170788
25-28 May 2024, Marseille Chanot, Marseille, France
