CONICET | Buscador de Institutos y Recursos Humanos

Gaucher disease is the most frequent of lysosomal storage diseases.This autosomic recessive disease is caused by mutations on the gene encoding for the lysosomal enzyme glucocerebrosidase. Deficiency of this enzyme leads to the accumulation of its substrate glucosylceramide, mainly in macrophages. Clinical manifestations include anemia, hepatosplenomegaly and bone alterations. On spite of treatment, bone alterations in Gaucher patients persist. Chitotriosidase is the most reliable biomarMer used in the folloY up of the disease, although its correlation Yith bone status has not been studied. Previous results suggest that osteoclasts are involved in bone tissue damage during the disease. The aim of our work was to study the pro osteoclastogenic potential in patients and to evaluate its correlation Yith chitotriosidase activity levels and clinical parameters. To evaluate the pro-osteoclastogenic state, PBMC from patients under Enzyme replacement Therapy were obtained by ficoll gradient and cultured in the presence of MCSF. Mature osteoclasts were defined as multinucleated TRAP positive cells. In the other hand, z-scores from bone densitometry total and column were analyzed in patients, as well as serum levels of CTX and chitotriosidase. As expected, serum chitotriosidase activity was higher in patients. We also found that osteoclast differentiation was increased in patients. HoYever, no correlation between osteoclasts and serum chitotriosidase was observed. Osteoclast levels presented a negative correlation with z score both total and column while a positive correlation with CTL was observed. +n conclusion, our results shoY for the first time a correlation betYeen osteoclast differentiation and bone clinical parameters in )aucher disease, but not betYeen osteoclasts and chitotriosidase. In addition, these results support the involvement of osteoclasts in the bone pathology of )aucher disease