Increased circulating levels of osteoclast precursors in Gaucher disease patients: Implicances for bone pathology

MUCCI J M; CUELLO M; KISINOVSKY I; LARROUDE M; DE FRANCESCO P N; DELPINO M V; ROZENFELD P A

Orlando, FL

Congreso; Lysosomal Disease Network's 9th Annual WORLD Symposium,; 2013

Lysosomal Disease Network

Pathological mechanisms of skeletal manifestations of Type I Gaucher disease (GD), are still poorly understood. Inflammation is a key factor and increased bone resorption markers have been described in patients. RANKLOPGRANK axis has been described as the central regulator of osteoclast differentiation. Previous results from our group showed an increase in osteoclastogenesis in our in vitro GD model. The aim of this study is to evaluate the presence of circulating osteoclast precursors (OP), along with the expression of surface molecules in lymphocytes from blood of patients with GD. PBMC were cultured in the presence of M-CSF and osteoclast differentiation was determined by counting TRAP positive multinucleated cells. IL-1 , TNF- and IL-6 levels were determined in culture supernatants of PBMC by ELISA. Patients showed a higher percentage of CD14 + CD16 + CD51 + (15.4 ± 2.5 vs 11 ± 5.9%) as well as higher average fluorescence of RANKL in T lymphocytes (1.15 ± 0.07 fold Increase p < 0.05). Osteoclast differentiation was also increased 4 times in patients (p < 0.05). Cytokine levels in supernatants were slightly increased for patients. Our findings show a greater presence of OP in circulation of patients with GD and an increased osteoclast differentiation capability as well as increased expression of RANKL in LT, which could contribute to bone involvement in patients. Increased levels of cytokines could generate a positive feedback on osteoclast generation process. This work was supported by a grant from Shire HGT (USA) [IIR-ARG-000120 to PR].