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Bone differentiation defects have been recently tied to Wnt signaling alterations occurring in vitro and in vivo Gaucher disease models. In this work, we provide evidence that the Wnt signaling multi-domain intracellular transducers DISHEVELLED 1 and 2 (DVL1 and DVL2) may be potential upstream targets of impaired beta glucosidase (GBA1) activity by showing their misexpression in different type 1 Gaucher disease in vitro models. We also show that in Gba mutant fish a miR-221 upregulation is associated with reduced dvl2 expression levels and that in type I Gaucher patients single nucleotide variants (SNVs) in the DVL2 3'UTR are related to variable canonical Wnt pathway activity. Thus, we strengthen the recently outlined relation between bone differentiation defects and Wnt/β-catenin dysregulation in type I Gaucher disease, and further propose novel mechanistic insights of the Wnt pathway impairment caused by glucocerebrosidase loss of function.
PMID: 31816052 [PubMed - as supplied by publisher]