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Cultured circulating mononuclear cells from osteopetrotic infants express the osteoclast‐associated vitronectin receptor and form multinucleated cells in response to 1,25‐dihydroxyvitamin D 3
Author(s) -
Cournot Giulia,
Petrovic Milka,
Trubert ClaireLise,
Cormier Catherine,
Girault Danielle,
Fischer Alain,
Garabedian MichÈLe
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080109
Subject(s) - osteopetrosis , osteoclast , peripheral blood mononuclear cell , multinucleate , haematopoiesis , bone marrow , vitronectin , medicine , calcitonin , endocrinology , cord blood , stem cell , lymphopoiesis , calcitonin receptor , biology , microbiology and biotechnology , chemistry , pathology , immunology , receptor , in vitro , biochemistry , integrin , neuropeptide , calcitonin gene related peptide
Abstract Malignant osteopetrosis is characterized by impaired osteoclast activity. Osteoclasts derive from hematopoietic stem cells. In osteopetrosis, marrow cavities fail to develop, resulting in extramedullary hematopoiesis and the presence of stem cells in the bloodstream. Resistance to 1,25‐(OH) 2 D 3 may be involved in the pathogenesis of the disease. Sensitivity to 1,25‐(OH) 2 D 3 , calcitonin sensitivity, and expression of the osteoclast‐associated vitronectin receptor (VR) was examined in cultures of circulating mononuclear cells of seven osteopetrotic infants (1.5–6 months old). Since peripheral blood from age‐matched children contains few stem cells, umbilical cord blood was used as control. Mononucleated cells were isolated by the Ficoll‐Hypaque method and cultured (10 6 cells per ml) in α‐MEM containing 20% horse serum in presence or absence of added 1,25‐(OH) 2 D 3 . VR was identified by immunochemical staining with MAb 23C6. 1,25‐(OH) 2 D 3 at 10 −8 M significantly stimulated the formation of multinucleated cells (MNC) in cultures from all osteopetrotic patients and cord blood samples. Cells from three of five patients responded to 10 −9 M 1,25‐(OH) 2 D 3 , the minimal stimulatory concentration for cord blood. Salmon calcitonin (100 ng/ml) partially inhibited the 10 −8 M 1,25‐(OH) 2 D 3 ‐induced MNC formation in cultures from three of six patients and in cultures of all cord blood samples. In both types of cultures mononuclear cells and MNC cross‐reacted with MAb 23C6, and 1,25‐(OH) 2 D 3 concentration did not influence the number and percentage of these cells. This study does not support the hypothesis of 1,25‐(OH) 2 D 3 resistance in osteopetrotic infants and shows that mononuclear cells expressing VR, possibly osteoclast progenitors, develop in cultures of circulating mononuclear cells from these infants. 1,25‐(OH) 2 D 3 may not be closely involved in VR expression.