Heme oxygenase-1 protects human periodontal ligament cells against substance P-induced RANKL expression.
J Periodontal Res
; 45(3): 367-74, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20337895
ABSTRACT
BACKGROUND AND OBJECTIVE:
Although substance P (SP) stimulates bone resorption activity and this is reported to be correlated with the degree of periodontal inflammation, it is unclear how human periodontal ligament cells regulate neuropeptide-induced osteoclastogenesis or the possible involvement of heme oxygenase-1 (HO-1) might be. This study examines how SP affects osteoprotegerin (OPG) and RANKL expression via HO-1. MATERIAL ANDMETHODS:
Using immortalized human periodontal ligament cells, the effects of SP on the expression of HO-1, RANKL and OPG mRNA and proteins were determined by RT-PCR and western blotting, respectively. Various concentrations of SP (10(-7), 10(-8), 10(-9) and 10(-10) m) were added to the medium, and the cells were treated for 0, 0.25, 0.5, 1, 2 and 3 d.RESULTS:
Substance P upregulated RANKL and HO-1 and downregulated OPG mRNA and protein expression in periodontal ligament cells, in a concentration- and time-dependent manner. A HO-1 inducer inhibited both the upregulation of RANKL expression and downregulation of OPG expression by SP in periodontal ligament cells. By contrast, treatment with a HO-1 inhibitor or HO-1 small interferring RNA (siRNA) enhanced SP-stimulated RANKL expression. Inhibitors of ERK and p38 MAP kinases, phosphoinositide 3-kinase and nuclear factor-kappaB blocked the effects of SP on RANKL expression in periodontal ligament cells.CONCLUSION:
These results suggest that SP stimulates osteoclastic differentiation by increasing the expression of RANKL vs. OPG via the HO-1 pathway in periodontal ligament cells. The HO-1 pathway may be an effective therapeutic target for inhibiting chronic periodontitis involving alveolar bone resorption.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligamento Periodontal
/
Substância P
/
Heme Oxigenase-1
/
Ligante RANK
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article