Bone Abstracts

Dysfunctions of osteoclasts are the pathophysiological hallmark of osteopetrosis (OP). OP is a group of rare inherited human diseases caused by mutations in at least seven different genes. All OP forms are clinical characterized by enhanced bone density. The most severe form infantile OP usually presents with hematological impairment, in particular anemia and thrombocytopenia associated with extra medullary hematopoiesis, leukocytosis and hepatosplenomegaly.<p class="abste...

Osteoclast-poor autosomal recessive osteopetrosis is characterised by susceptibility to fracture despite high bone mineral density as a consequence of an absence of osteoclasts. One of the 12 receptor activator of NF-κB (RANK) mutations associated with this condition is a frameshift mutation encoding a protein that is truncated within the extracellular, N-terminal domain (R110Pfs). We investigated the effect of this mutation on osteoclast formation, receptor localisation ...

Twelve different mutations in TNFRSF11A (encoding the RANK receptor) have been associated with osteoclast-poor autosomal recessive osteopetrosis in patients. Two truncated RANK proteins resulting from substitution mutations (W434X and G280X), identified in two infants, cause loss of the intracellular oligomerisation motif and in the case of the G280X mutation the TRAF6 binding domain. A third mutation was identified in a 10-year-old patient and is a frameshift mutatio...

Infantile malignant osteopetrosis (IMO) is a rare, lethal, recessive disorder characterized by dysfunctional osteoclasts. TCIRG1, encoding the osteoclast V-ATPase, is mutated in 50% of IMO patients. We have previously shown that the resorptive function in osteoclasts derived from IMO patients can be restored in vitro by expressing TCIRG1 using a lentiviral vector. In this study, we aim to investigate the cellular response to vector-derived TCIRG1 expression and to det...