Osteochondroma formation is independent of heparanase expression as revealed in a mouse model of hereditary multiple exostoses.

ABSTRACT: Hereditary multiple exostoses (HME) is a rare, pediatric disorder characterized by osteochondromas that form along growth plates and provoke significant musculoskeletal problems. HME is caused by mutations in heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. Seemingly paradoxically, osteochondromas were found to contain excessive extracellular heparanase (Hpse) that could further reduce HS levels and exacerbate pathogenesis. To test Hpse roles, we asked whether its ablation would protect against osteochondroma formation in a conditional HME model consisting of mice bearing floxed Ext1 alleles in Agr-CreER background (Ext1^f/f ;Agr-CreER mice). Mice were crossed with a new global Hpse-null (Hpse^-/- ) mice to produce compound Hpse^-/- ;Ext1^f/f

SUBMITTER: Mundy C 

PROVIDER: S-EPMC9259764 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature