Evaluation of PPS treatment in osteoclast-osteoblast imbalance using in vitro models of Gaucher disease

MUCCI JUAN MARCOS; BONDAR, CONSTANZA M.; CRIVARO, ANDREA N.; ORMAZABAL, MAXIMILIANO E.; SCHUCHMAN, EDWARD; SIMONARO, CALOGERA; ROZENFELD, PAULA A.

Orlando

Congreso; 15th ANNUAL WORLD Symposium 2019; 2019

Gaucher disease (GD) is caused by mutations in the gene encoding for the lysosomal enzyme glucocerebrosidase. Bone alterations are the most disabling condition in Type I GD (GD1) patients and remain a chronic issue in spite of enzyme replacement therapy. Mechanisms leading to bone damage are poorly understood, but previous reports suggest that both osteoblasts and osteoclasts are involved. In the last years, several works have been published in relation to cartilage and bone pathology in mucopolysaccharidoses where inflammation was shown to be a key factor in pathogenesis. A compound called pentosan polysulphate (PPS) was proposed as therapy in MPS models and showed marked improvements in clinical behavior. In the present study we analyzed the effect of PPS treatment on osteoclast differentiation and osteoblast activity using in vitro models of GD. PPS treatment reduced osteoclast differentiation from GD patient PBMCs. Supernatants from two in vitro models of GD osteoblasts (MC3T3) and osteocytes (MLO-Y4) with CBE were obtained in the presence or absence of PPS. When osteoclast precursors were cultured in the presence of these supernatants, the PPS supernatants induced less osteoclast differentiation. Osteoblast activity was also improved by PPS treatment in these in vitro models. In addition, mineral deposition was increased in PPS treated osteoblasts. Our results suggest that PPS should be considered as an alternative treatment for bone implications in GD.