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WP1

Cartilage diseases in ageing

Osteoarthritis (OA) is the most common joint disease worldwide and one of the most frequent causes of physical disability among older adults. Among those aged over 65 years, ~48% of women and ~31%of men are affected. Precocious osteoarthritis (OA), a typical ageing signature, is a common feature of chondrodysplasias, genetic disorders of the skeleton due to defects in genes important for the development, growth and homeostasis of cartilage.

 

In WP1, the ESRs will:

 

  • dissect the OA phenotype in a mouse model of Diastrophic dysplasia (DC2),

  • generate a surgically induced osteoarthritis murine model (DC4), 

  • investigate the role of the aging autonomic nervous system in intervertebral disc and facet joint degeneration (DC5),

  • develop an ex vivo osteo-chondro ageing model (DC9),

  • dissect the OA phenotype in a mouse model of Spondyloepimetaphyseal dysplasia with joint laxity type II (DC11).

The specific OA mechanisms and markers identified in the monogenic disorders will be evaluated in light of data collected by DC4 as mechanisms of common OA related to ageing by deep phenotyping of cartilage biopsies from wild-type mice that underwent the destabilization of the medial meniscus (DMM) and of results obtained by DC9 using the osteo-chondro model on cartilage biopsies of OA patients undergoing joint replacement surgery. This ex vivo osteo-chondro model will be employed to study ageing-related cartilage and bone diseases, to study the effect of treatments and therapies developed within this project on human OA biopsies and to test whether modulation of the mechanical environment can be used to treat diseased cartilage and/or bone. In the same in vivo and ex vivo models, cellular senescence and the senescence associated phenotype will be studied in collaboration with DCs of WP4. The architecture and bone quality as well as the sarcopenia in the mouse models mentioned above will be studied during ageing through WP2 and WP3, respectively, since OA markedly affects movements, thus compromising the musculoskeletal system as a whole.

WP Lead: LifeTec Grouo

Doctoral candidates:

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