INVESTIGADORES
FOSSATI Carlos Alberto
artículos
Título:
Uncoupling of osteoblast/osteoclast regulation in a chemical murine model of Gaucher disease
Autor/es:
MUCCI JM; SUQUELI GARCIA F; DE FRANCESCO PN,; CECI R; DE GENARO S; FOSSATI CA; DELPINO MV; ROZENFELD, PA
Revista:
GENE
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 532 p. 186 - 191
ISSN:
0378-1119
Resumen:
Gaucher disease (GD) is caused by mutations in the GBA
gene that confer a deficient level of activity of
glucocerebrosidase (GCase). This deficiency leads to accumulation of the
glycolipid glucocerebroside in the lysosomes of cells ofmonocyte/macrophage
system. Type I GDis the mildest formand is characterized by the absence of
neuronopathic affection. Bone compromise in Gaucher disease patients is the
most disabling aspect of the disease. 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 formation by osteoblasts. We decided to test whether bone resorption and/or
bone formation could be altered by the 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 osteoclasts precursors from bone marrow to
mature and functional osteoclasts. TNF-α could be one of the factors responsible
for this effect. On the other hand, addition of CM to an osteoblast cell
culture resulted in a reduction in expression of alkaline phosphatase and
mineralization process. In conclusion, these results suggest implication of
changes in both bone formation and bone resorption and are consistent with the
idea that both sides of the homeostatic balance are affected in GD