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- Title
Heme oxygenase-1 protects human periodontal ligament cells against substance P-induced RANKL expression.
- Authors
Lee, H.‐J.; Jeong, G.‐S.; Pi, S.‐H.; Lee, S.‐I.; Bae, W.‐J.; Kim, S.‐J.; Lee, S.‐K.; Kim, E.‐C.
- Abstract
Lee H-J, Jeong G-S, Pi S-H, Lee S-I, Bae W-J, Kim S-J, Lee S-K, Kim E-C. Heme oxygenase-1 protects human periodontal ligament cells against substance P-induced RANKL expression. J Periodont Res 2010; 45: 367–374. © 2010 John Wiley & Sons A/S 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 and Methods: 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-κB 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.
- Subjects
NEUROTRANSMITTERS; INFLAMMATORY mediators; MESSENGER RNA; BONE resorption; BONE diseases
- Publication
Journal of Periodontal Research, 2010, Vol 45, Issue 3, p367
- ISSN
0022-3484
- Publication type
Article
- DOI
10.1111/j.1600-0765.2009.01247.x