Osteoblast and adipose differentiation of Gaucher mesenchymal stem cells

CRIVARO, ANDREA; BONDAR, CONSTANZA; MUCCI, JUAN MARCOS; ORMAZABAL, MAXIMILIANO; FELDMAN, ROBERTO; DELPINO, VICTORIA; ROZENFELD, PAULA

Simposio; World Symposium 2019; 2019

Gaucher disease (GD) is caused by mutations in GBA gene thatencodes the lysosomal enzyme glucocerebrosidase. Type I GD (GD1)patients present visceral, hematological and bone problems. Up tonow, specific treatment for GD cannot completely reverse boneproblems. Bone is a dynamic tissue that is continuously remodelingin order to maintain proper structure. It is composed by hematopoieticcells as machrophages and non hematopoietic cells as mesenchymalstem cells (MSCs). The first group is able to differentiate intoosteoclasts in presence of MCS-F and RANKL, and the other one giverise to chondrocytes, osteoblasts and adipocytes, so an imbalancebetween these cells could lead to bone disease. The aim of this workis to evaluate the potential of MSCs from GD and control patients todifferentiate towards osteoblast (GDOb) and adipocyte (GDAd)lineages, as well as its effect in osteoclast formation. We observedreduced mineralization, collagen deposition and alkaline phosphataseactivity when MSCs from GD were cultured in osteogenicdifferentiation media. Moreover, the expression of osteoblasticdifferentiation markers ColA1, ALP, BMP-2 and Runx2 was lower inGD cells. On the other hand, we cultured THP-1 cells with MCS-F andconditioned media obtained from Control and GDOb to evaluate theinduction of osteoclast formation. We observed an increase numberof osteoclasts number when GDOb conditioned media was usedcompared to Control. Furthermore, adipogenic differentiation revealedthat GDAd produced lower levels of lipid droplets thanControl Ad. In conclusion, our results show an alteration in GD MSCsdifferentiation 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 skeletalimbalance in GD.