IDEHU   05542
INSTITUTO DE ESTUDIOS DE LA INMUNIDAD HUMORAL PROF. RICARDO A. MARGNI
Unidad Ejecutora - UE
artículos
Título:
Uncoupling of osteoblast-osteoclast regulation in a chemical murine model of Gaucher disease.
Autor/es:
MUCCI J M; SUQUELI GARCIA M F; DE FRANCESCO P N; CECI R; DI GENARO S; FOSSATI C A; DELPINO M V; ROZENFELD P A; MUCCI J M; SUQUELI GARCIA M F; DE FRANCESCO P N; CECI R; DI GENARO S; FOSSATI C A; DELPINO M V; ROZENFELD P A
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 of monocyte/macrophage
system. Type I GD is the mildest form and 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 is
maintained 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 peritoneal macrophages (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.