Speaker: Dr Kazuhiro Yamamoto, Kennedy Institute of Rheumatology, University of Oxford
Venue: Room L2.6, William Leech Building, Medical School
Date and time: 10-11am Friday 24th October 2014
Dr Kazuhiro Yamamoto will present:
‘’The Regulation of Cartilage Tissue Catabolism by the Endocytic Receptor LRP1’’
Cartilage degradation in osteoarthritis (OA) is now well established to be the result of elevated proteinase activities, with the key enzymes being aggrecanases and collagenases. Aggrecanase activities are post-translationally regulated by prodomain removal, C-terminal processing and inhibition by the endogenous inhibitor, tissue inhibitor of metalloproteinases (TIMP)-3. My recent study showed that low-density lipoprotein receptor-related protein 1 (LRP1)-mediated endocytic process is also an important regulator of aggrecanases (ADAMTS-4 and ADAMTS-5) and collagenase 3 (MMP-13), in normal healthy cartilage. However, this process is impaired in OA cartilage due to increased shedding of LRP1, which results in increased extracellular activities of aggrecanases and MMP-13. I will talk about how I discover the novel endocytic pathway and its impact on cartilage tissue catabolism. I will also focus on my current and future approaches to investigate how tissue maintains extracellular matrix homeostasis by controlling tissue-degrading proteinases and how tissue loses the homeostasis with ageing and pathological conditions.
Tissue catabolism; Osteoarthrits; Endocytosis; Extracellular trafficking; Metalloproteinases.