Calcium-containing crystals enhance receptor activator of nuclear factor κB ligand/macrophage colony-stimulating factor-mediated osteoclastogenesis via extracellular-signal-regulated kinase and p38 pathways.
Rheumatology (Oxford)
; 54(10): 1913-22, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-25998451
ABSTRACT
OBJECTIVE:
Diseases associated with calcium-containing crystal deposition can lead to local bone erosion. We aimed to determine whether calcium-containing crystal-hydroxyapatite, ß-tricalcium phosphate and CPPD enhanced osteoclastogenesis and to define underlying mechanisms of action.METHODS:
Osteoclastogenesis was studied by culturing murine RAW 264.7 osteoclast precursor cells with RANK ligand (RANKL)/ M-CSF and/or calcium-containing crystals, and observing the tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and TRAP activity. Resorption pit formation was used to evaluate osteoclast activity. Real-time RT-PCR analysis revealed osteoclast marker genes, including TRAP, cathepsin K and calcitonin receptor (CTR). Western blotting was used to analyse the phosphorylation levels of signal transduction molecules.RESULTS:
Three kinds of calcium-containing crystal significantly enhanced RANKL/M-CSF-induced osteoclastogenesis in RAW 264.7 cells, as evidenced by the increased number of TRAP-positive multinucleated cells, TRAP activity and resorption pit formation in a dose-dependent manner. Hydroxyapatite, ß-tricalcium phosphate and CPPD treatments significantly enhanced RANKL/M-CSF-induced mRNA expression of TRAP, cathepsin K and CTR. Moreover, the three kinds of calcium-containing crystal enhanced the phosphorylation of extracellular-signal-regulated kinase and p38 in RANKL/M-CSF-treated cells.CONCLUSION:
We concluded that calcium-containing crystals can promote osteoclastogenesis and bone resorption through the extracellular-signal-regulated kinase and p38 pathways. Together with synovial activation, this mechanism may be important in the pathogenesis of destructive arthropathies triggered by calcium-containing crystals.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteoclastos
/
Osteogénesis
/
Calcio
/
Factor Estimulante de Colonias de Macrófagos
/
Sistema de Señalización de MAP Quinasas
/
Quinasas MAP Reguladas por Señal Extracelular
/
Ligando RANK
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Rheumatology (Oxford)
Asunto de la revista:
REUMATOLOGIA
Año:
2015
Tipo del documento:
Article