Proinflammatory and proosteoclastogenic potential of peripheral blood mononuclear cells from Gaucher patients: implication for bone pathology

MUCCI JM; CUELLO F; KISINOVSKI I; LARROUDE M; DELPINO MV; ROZENFELD PA

BLOOD CELLS MOLECULES AND DISEASES

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2015 vol. 55 p. 134 - 143

1079-9796

Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity ofglucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in thelysosomes of cells of monocyte/macrophage system. Bone compromise in Gaucher disease patients is the mostdisabling aspect of the disease. However, pathophysiological aspects of skeletal alterations are still poorlyunderstood. On the other hand it is well known that inflammation is a key player in GD pathology. In thiswork, we revealed increased levels of the proinflammatory CD14+CD16+ monocyte subset and increasedinflammatory cytokine production by monocytes and T cells in the circulation of GD patients. We showedincreased levels of osteoclast precursors in PBMC from patients and a higher expression of RANKL in the surfaceof T cells. PBMC from patients presented higher osteoclast differentiation compared to healthy controls whencultured in the presence of M-CSF alone or in combination with RANKL. In vitro treatment with Velaglucerasereduced osteoclast levels to control levels. On the other hand THP-1 derived osteoclast precursors cultured inthe presence of conditioned media from PBMC of GD patients presented higher differentiation to activeosteoclasts. This induction involved TNF-α and RANKL.