Uncoupling of osteoblast-osteoclast regulation in a chemical murine model of Gaucher disease

MUCCI JM; SUQUELLI GARCIA, F; DE FRANCESCO, PN; CECI R; DI GENARO S; FOSSATI CA; DELPINO MV; ROZENFELD PA

GENE

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2013 vol. 532 p. 186 - 191

0378-1119

Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity ofglucocerebrosidase (GCase). This deficiency leads to accumulation of the glycolipid glucocerebroside in the lysosomesof cells ofmonocyte/macrophage system. Type I GDis the mildest formand is characterized by the absenceof neuronopathic affection. Bone compromise in Gaucher disease patients is the most disabling aspect of thedisease. However, pathophysiological aspects of skeletal alterations are still poorly understood.The homeostasis of bone tissue ismaintained by the balanced processes of bone resorption by osteoclasts and formationby osteoblasts. We decided to test whether bone resorption and/or bone formation could be altered bythe use of a chemical in vitro murine model of Gaucher disease.We used two sources of cells from monocyte/macrophages lineage isolated from normal mice, splenocytes (S)and peritonealmacrophages (PM), and were exposed to CBE, the inhibitor of GCase (S-CBE and PM-CBE, respectively).Addition of both conditioned media (CM) from S-CBE and PM-CBE induced the differentiation of osteoclastsprecursors from bone marrow to mature and functional osteoclasts. TNF-α could be one of the factorsresponsible for this effect. On the other hand, addition of CM to an osteoblast cell culture resulted in a reductionin expression of alkaline phosphatase and mineralization process. In conclusion, these results suggest implicationof changes in both bone formation and bone resorption and are consistent with the idea that both sides of thehomeostatic balance are affected in GD.