Oncostatin m, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury.
Am J Pathol
; 185(3): 765-75, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25559270
ABSTRACT
Different macrophage depletion strategies have demonstrated a vital role of macrophages in bone healing, but the underlying molecular mechanisms are poorly understood. Here, with the use of a mouse model of tibia injury, we found that the cytokine oncostatin M [OSM or murine (m)OSM] was overexpressed during the initial inflammatory phase and that depletion of macrophages repressed mOSM expression. In Osm(-/-) mice, by micro-computed tomography and histology we observed a significant reduction in the amount of new intramedullar woven bone formed at the injured site, reduced number of Osterix(+) osteoblastic cells, and reduced expression of the osteoblast markers runt-related transcription factor 2 and alkaline phosphatase. In contrast, osteoclasts were normal throughout the healing period. One day after bone injury, Stat3, the main transcription factor activated by mOSM, was found phosphorylated/activated in endosteal osteoblastic cells located at the hedge of the hematoma. Interestingly, we observed reduced activation of Stat3 in Osm(-/-) mice. In addition, mice deficient in the mOSM receptor (Osmr(-/-)) also had reduced bone formation and osteoblast number within the injury site. These results suggest that mOSM, a product of macrophages, sustains intramembranous bone formation by signaling through Osmr and Stat3, acting on the recruitment, proliferation, and/or osteoblast differentiation of endosteal mesenchymal progenitor cells. Because bone resorption is largely unaltered, OSM could represent a new anabolic treatment for unconsolidated bone fractures.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Osteoclastos
/
Tíbia
/
Oncostatina M
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article