The effect of podoplanin deficiency on bone structure

microCT images of wild-type and podoplanin KO mouse bones.

## Access ##
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Modified subchondral bone (SCB) modelling and thickening are hallmarks of osteoarthritis (OA) and unquestionably contribute to OA pathogenesis. Currently, there are no known ways to restrict increases in SCB mass. This proposal will test whether SCB thickening in OA can be restricted by promoting E11 protein stability to drive osteocyte formation (osteocytogenesis) and sclerostin-mediated inhibition of bone formation. This hypothesis stems from our pilot data revealing that osteocyte formation is triggered by matrix mineralisation in a pathway reliant on the expression and stabilisation of E11 protein. Using hypomineralisation murine models (phospho1-/-) and human osteoblasts our first goal will determine if matrix mineralisation drives E11 expression and osteocyte formation. The critical requirement for E11 expression to drive osteocytogenesis will be confirmed by studying mice harbouring an osteoblast deletion of E11. Furthermore, we will determine the post-translational mechanisms controlling osteocyte E11 protein stability and whether these can be targeted to accelerate osteocytogenesis. Finally, OA-like trauma will be induced by non-invasive loading to determine if SCB changes are characterised by aberrant mineralisation and disrupted osteocytogenesis and E11 expression. This proposal will identify a novel means of selectively minimising increases in SCB mass to slow joint deterioration and prolong life quality in OA patients.

Staines, K; Farquharson, C "The effect of podoplanin deficiency on bone structure" (2019) [dataset] Edinburgh DataVault10.7488/5acc1997-69be-496b-964b-f22ad06456d8 .