Osteoblast and adipose differentiation of Gaucher mesenchymal stem cells

CRIVARO, ANDREA N.; BONDAR, CONSTANZA M.; MUCCI, JUAN M.; ORMAZABAL, MAXIMILIANO E.; FELDMAN, RICARDO; DELPINO MARIA VICTORIA; ROZENFELD, PAULA A.

Orlando

Congreso; 15th ANNUAL WORLD Symposium 2019; 2019

Gaucher disease (GD) is caused by mutations in GBA gene that encodes the lysosomal enzyme glucocerebrosidase. Type I GD (GD1) patients present visceral, hematological and bone problems. Up to now, specific treatment for GD cannot completely reverse bone problems. Bone is a dynamic tissue that is continuously remodeling in order to maintain proper structure. It is composed by hematopoietic cells as machrophages and non hematopoietic cells as mesenchymal stem cells (MSCs). The first group is able to differentiate into osteoclasts in presence of MCS-F and RANKL, and the other one give rise to chondrocytes, osteoblasts and adipocytes, so an imbalance between these cells could lead to bone disease. The aim of this work is to evaluate the potential of MSCs from GD and control patients to differentiate towards osteoblast (GDOb) and adipocyte (GDAd) lineages, as well as its effect in osteoclast formation. We observed reduced mineralization, collagen deposition and alkaline phosphatase activity when MSCs from GD were cultured in osteogenic differentiation media. Moreover, the expression of osteoblastic differentiation markers ColA1, ALP, BMP-2 and Runx2 was lower in GD cells. On the other hand, we cultured THP-1 cells with MCS-F and conditioned media obtained from Control and GDOb to evaluate the induction of osteoclast formation. We observed an increase number of osteoclasts number when GDOb conditioned media was used compared to Control. Furthermore, adipogenic differentiation revealed that GDAd produced lower levels of lipid droplets than Control Ad. In conclusion, our results show an alteration in GD MSCs differentiation process towards osteoblast and adipose lineages, being BMP-2 pathway implicated in the altered osteoblast differentiation. Besides, GDOb demonstrate to be able to induce osteoclastogenesis. These changes in GD MSCs could contribute to skeletal imbalance in GD.