Osteoclastogenesis Functional Study of Osteoclasts Precursors from Gaucher Disease Patients

MUCCI JM; CUELLO F; KISINOVSKI I; LARROUDE M; DELPINO MV; ROZENFELD PA

San Diego

Congreso; Lysosomal Disease Network-10th Annual WORLD Symposium; 2014

LDN

Pathological mechanisms of skeletal manifestations of Type I Gaucher disease (GD), including osteopenia and osteonecrosis, are still poorly understood. Inflammation is a key factor in the pathogenesis of GD and increased bone resorption markers have been described in patients. RANKL \ OPG \ RANK axis has been described as the central regulator of osteoclast differentiation. Previous results from our group showed an increase in circulating osteoclast precursors in blood from GD patients and higher differentiation towards TRAP+ cells. In addition we have revealed that the addition of conditioned media (CM) from GD patients´PBMC induced higher osteoclastogenesis levels, and this process was partially mediated by TNF-α and RANKL. The aim of this study is to characterize osteoclast resorption activity from GD patients´cells and assess the effect of velaglucerase alfa (VPRIV? , SHire, USA) on osteoclast differentiation. PBMC were cultured in the presence of M-CSF on dentine covered wells and osteoclast activity was determined by counting pit formation. The same experiment was carried out but in the presence of velaglucerase alfa and osteoclast differentiation was assessed by counting TRAP positive multinucleated cells. Osteoclast precursors obtained from THP-1 cells were stimulated with CM in the presence of a TNF-α neutralizing antibody or osteoprotegerin (OPG) and resorption activity was studied. Number of resorption pits obtained from GD PBMC was increased 4 times as compared to normal controls PBMC (p