Bone Abstracts

Familial expansile osteolysis (FEO) is characterised by focal areas of increased bone turnover driven by bone-resorbing osteoclasts. The syndrome is caused by a heterozygous tandem insertion duplication mutation within the signal peptide region of TNFRSF11a (encoding receptor activator of NFκB; RANK). Our recent research has demonstrated that heterotrimeric receptor formation may hold the key to the disease phenotype. We have shown previously that, whilst homozygous overe...

Early-onset Paget’s disease of bone (ePDB), familial expansile osteolysis (FEO) and expansile skeletal hyperphosphatasia (ESH) are related syndromes caused by heterozygous tandem insertion duplication mutations within the signal peptide region of TNFRSF11a (encoding receptor activator of NFκB; RANK). Given that patients are always heterozygous for these mutations we have generated thirteen cell lines to investigate the molecular consequences of these mutations in...

The interaction of Receptor Activator of NFkB ligand (RANKL) with its cognate receptor RANK is crucial for osteoclast formation. We studied eight point mutations within human RANK associated with rare forms of osteopetrosis to gain mechanistic insights into the regulation of RANK signalling.We investigated the role of the oligomerisation domain within the cytoplasmic region of RANK studying two mutations (W434X and G280X) identified in rare cases of oste...