Heme oxygenase‐1 protects human periodontal ligament cells against substance P‐induced RANKL expression

• Published in: Journal of periodontal research Vol. 45; no. 3; pp. 367 - 374
• Main 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.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-2010
• Subjects: Cell Differentiation - drug effects; Cell Line; Cell Nucleus - chemistry; Cytosol - chemistry; Dentistry; Dose-Response Relationship, Drug; Enzyme Induction; Enzyme Inhibitors - pharmacology; Heme Oxygenase-1 - antagonists & inhibitors; Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - pharmacology; heme oxygenase‐1; Hemin - pharmacology; Humans; Mitogen-Activated Protein Kinases - antagonists & inhibitors; NF-E2-Related Factor 2 - analysis; NF-kappa B - antagonists & inhibitors; Osteoclasts - drug effects; osteoprotegerin; Osteoprotegerin - drug effects; Osteoprotegerin - metabolism; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; Periodontal Ligament - cytology; Periodontal Ligament - drug effects; periodontal ligament cell; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Protoporphyrins - pharmacology; RANK Ligand - drug effects; RANK Ligand - metabolism; receptor activator of nuclear factor‐κB ligand; RNA, Small Interfering - pharmacology; substance P; Substance P - administration & dosage; Substance P - pharmacology; Time Factors
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/j.1600-0765.2009.01247.x

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.