INF-γ encoding plasmid administration triggers bone loss and disrupts bone marrow microenvironment.
J Endocrinol
; 232(2): 309-321, 2017 02.
Article
em En
| MEDLINE
| ID: mdl-27908965
ABSTRACT
IFN-γ is a pleotropic cytokine produced in the bone microenvironment. Although IFN-γ is known to play a critical role on bone remodeling, its function is not fully elucidated. Consistently, outcomes on the effects of IFN-γ recombinant protein on bone loss are contradictory among reports. In our work we explored, for the first time, the role of IFN-γ encoding plasmid (pIFN-γ) in a mouse model of osteopenia induced by ovariectomy and in the sham-operated counterpart to estimate its effects in skeletal homeostasis. Ovariectomy produced a dramatic decrease of bone mineral density (BMD). pINF-γ injected mice showed a pathologic bone and bone marrow phenotype; the disrupted cortical and trabecular bone microarchitecture was accompanied by an increased release of pro-inflammatory cytokine by bone marrow cells. Moreover, mesenchymal stem cells' (MSCs) commitment to osteoblast was found impaired, as evidenced by the decline of osterix-positive (Osx+) cells within the mid-diaphyseal area of femurs. For instance, a reduction and redistribution of CXCL12 cells have been found, in accordance with bone marrow morphological alterations. As similar effects were observed both in sham-operated and in ovariectomized mice, our studies proved that an increased IFN-γ synthesis in bone marrow might be sufficient to induce inflammatory and catabolic responses even in the absence of pathologic predisposing substrates. In addition, the obtained data might raise questions about pIFN-γ's safety when it is used as vaccine adjuvant.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Ósseas Metabólicas
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Medula Óssea
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Densidade Óssea
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Interferon gama
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Remodelação Óssea
Limite:
Animals
Idioma:
En
Revista:
J Endocrinol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália