Enhanced osteoclastogenesis by Gaucher disease patients´ mononuclear cells: implicances for bone pathology

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

Buenos Aires

Congreso; V Congreso Latinoamericano de Enfermedades Lisosomales; 2013

COLATEL

Pathological mechanisms of skeletal manifestations of Type I Gaucher disease (GD), including osteopenia and osteonecrosis, are still poorly understood. Inflammation is a key factor in the pathogenesis of GD and increased bone resorption markers have been described in patients. RANKL OPG RANK 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) and its differentiation potential, along with the expression of the surface molecule RANKL in lymphocytes from blood of patients with GD. Percentage of OP and RANKL levels in PBMC were analyzed in GD patients and controls, based on the expression of CD16, CD14 and CD51, and CD3, CD20 and RANKL, respectively. In addition, PBMC were cultured in the presence of M-CSF and osteoclast differentiation was determined by counting TRAP positive multinucleated cells. IL-1β, TNF-α 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). Cytokines 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.