1. Proinflammatory and proosteoclastogenic potential of peripheral blood mononuclear cells from Gaucher patients: Implication for bone pathology
- Author
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Juan Marcos Mucci, Isaac Kisinovsky, Paula Rozenfeld, María Victoria Delpino, Maria Silvia Larroude, and María Fernanda Cuello
- Subjects
Adult ,Male ,musculoskeletal diseases ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Adolescent ,medicine.medical_treatment ,Genética Humana ,Osteoclasts ,Glucocerebroside ,Bone and Bones ,Immunophenotyping ,Proinflammatory cytokine ,Young Adult ,GAUCHER DISEASE ,Osteoclast ,Internal medicine ,medicine ,Humans ,Macrophage ,Bone Resorption ,Child ,Molecular Biology ,Aged ,Gaucher Disease ,biology ,Monocyte ,OSTEOCLASTS ,Cell Differentiation ,Cell Biology ,Hematology ,Middle Aged ,Medicina Básica ,medicine.anatomical_structure ,Endocrinology ,Cytokine ,RANKL ,Antigens, Surface ,Immunology ,Leukocytes, Mononuclear ,biology.protein ,Cytokines ,OSTEOIMMUNOLOGY ,Molecular Medicine ,Female ,BONE PATHOLOGY ,Inflammation Mediators ,Glucocerebrosidase ,GLUCOCEREBROSIDASE DEFICIENCY - Abstract
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 the accumulation of the glycolipid glucocerebroside in the lysosomes of cells of monocyte/macrophage system. Bone compromise in Gaucher disease patients is the most disabling aspect of the disease. However, pathophysiological aspects of skeletal alterations are still poorly understood. On the other hand it is well known that inflammation is a key player in GD pathology. In this work, we revealed increased levels of the proinflammatory CD14+CD16+ monocyte subset and increased inflammatory cytokine production by monocytes and T cells in the circulation of GD patients. We showed increased levels of osteoclast precursors in PBMC from patients and a higher expression of RANKL in the surface of T cells. PBMC from patients presented higher osteoclast differentiation compared to healthy controls when cultured in the presence of M-CSF alone or in combination with RANKL. In vitro treatment with Velaglucerase reduced osteoclast levels to control levels. On the other hand THP-1 derived osteoclast precursors cultured in the presence of conditioned media from PBMC of GD patients presented higher differentiation to active osteoclasts. This induction involved TNF-α and RANKL. Fil: Mucci, Juan Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Cuello, María Fernanda. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Kisinovsky, Isaac. Instituto Médico Quilmes; Argentina Fil: Larroude, María Silvia. Consultorio Larrea ; Argentina Fil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
- Published
- 2015
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