title: Sodium hydrogen sulfide inhibits nicotine and lipopolysaccharide-induced osteoclastic differentiation and reversed osteoblastic differentiation in human periodontal ligament cells.
abstract: Although previous studies have demonstrated that hydrogen sulfide (H(2)S) stimulated or inhibited osteoclastic differentiation, little is known about the effects of H(2)S on the differentiation of osteoblasts and osteoclasts. To determine the possible bioactivities of H(2)S on bone metabolism, we investigated the in vitro effects of H(2)S on cytotoxicity, osteoblastic, and osteoclastic differentiation as well as the underlying mechanism in lipopolysaccharide (LPS) and nicotine-stimulated human periodontal ligament cells (hPDLCs). The H(2)S donor, NaHS, protected hPDLCs from nicotine and LPS-induced cytotoxicity and recovered nicotine- and LPS-downregulated osteoblastic differentiation, such as alkaline phosphatase (ALP) activity, mRNA expression of osteoblasts, including ALP, osteopontin (OPN), and osteocalcin (OCN), and mineralized nodule formation. Concomitantly, NaHS inhibited the differentiation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in mouse bone marrow cells and blocked nicotine- and LPS-induced osteoclastogenesis regulatory molecules, such as RANKL, OPG, M-CSF, MMP-9, TRAP, and cathepsin K mRNA. NaHS blocked nicotine and LPS-induced activation of p38, ERK, MKP-1, PI3K, PKC, and PKC isoenzymes, and NF-κB. The effects of H(2)S on nicotine- and LPS-induced osteoblastic and osteoclastic differentiation were remarkably reversed by MKP-1 enzyme inhibitor (vanadate) and expression inhibitor (triptolide). Taken together, we report for the first time that H(2)S inhibited cytotoxicity and osteoclastic differentiation and recovered osteoblastic differentiation in a nicotine- and periodontopathogen-stimulated hPDLCs model, which has potential therapeutic value for treatment of periodontal and inflammatory bone diseases.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Chung
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Choi
authors.forename: Q-Schick
authors.initials: QS
authors.lastname: Auh
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Lee
authors.forename: Sang-Im
authors.initials: SI
authors.lastname: Lee
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D003470:Culture Media / Q000737:chemistry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010513:Periodontal Ligament / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D003470:Culture Media; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013440:Sulfides; D009538:Nicotine; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C025451:sodium bisulfide