OSTEOIMMUNOLOGY IN GAUCHER DISEASE: TNF-ALPHA INVOLVEMENT ON AN IN VITRO MURINE MODEL

MUCCI JUAN M; DE FRANCESCO P N; CECI ROMINA; DI GENARO SILVIA; DELPINO M VICTORIA; ROZENFELD PAULA

Congreso; 42. LXI Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 4-7 Noviembre 2013.; 2013

Gaucher disease (GD) is a genetic lysosomal storage disorder caused by the deficiency of the enzyme beta-glucosidase (GBA). Skeletal manifestations in GD include osteopenia and osteonecrosis, and are the most disabling aspect of the disease, causing high morbidity and a significant decrease in quality of life. Inflammation is a key factor in the pathogenesis of GD. Previous results from our group showed an increase in osteclastogenesis in our human in vitro model of the GD with involvement of T cells and TNF-α as a soluble mediator. In the present work we aimed to test an in vitro model of GD using mouse cells to correlate our previous findings. We used two sources of cells from monocyte/machrophages lineage isolated from normal mice, splenocytes (S) and peritoneal machrophages (PM), and were exposed to CBE, the inhibitor of GCase (S-CBE and MP-CBE, respectively). Addition of both conditioned media (CM) from S-CBE and PM-CBE induced the differentiation of osteoclasts precursors from bone marrow (BMP) to mature and functional osteoclasts (p<0,01) as shown by TRAP staining, resorption activity and matrix metalloproteinases. TNF-α could be one of the factors responsible for this effect. The use of BMP from TNFRp55 KO mice sowed a decrease on osteoclast number and resorptive activity (p<0,05). On the other side, addition of CM to an osteoblast cell culture resulted in a reduction in expression of alkaline phosphatase and mineralization process (p< 0,01). 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.