title: Increased apoptosis in osteoclasts and decreased RANKL immunoexpression in periodontium of cimetidine-treated rats.
abstract: It has been demonstrated that histamine interferes with the recruitment, formation and activity of osteoclasts via H(1)- and H(2)-receptors. Cimetidine is a H(2)-receptor antagonist used for treatment of gastric ulcers that seems to prevent bone resorption. In this study, a possible cimetidine interference was investigated in the number of alveolar bone osteoclasts. The incidence of osteoclast apoptosis and immunoexpression of RANKL (receptor activator of nuclear factor κB ligand) was also evaluated. Adult male rats were treated with 100 mg kg(-1) of cimetidine for 50 days (CimG); the sham group (SG) received saline. Maxillary fragments containing the first molars and alveolar bone were fixed, decalcified and embedded in paraffin. The sections were stained by H&E or submitted to tartrate-resistant acid phosphatase (TRAP) method. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) method and immunohistochemical reactions for detecting caspase-3 and RANKL were performed. The number of TRAP-positive osteoclasts, the frequency of apoptotic osteoclasts and the numerical density of RANKL-positive cells were obtained. Osteoclast death by apoptosis was confirmed by transmission electron microscopy (TEM). In CimG, TRAP-positive osteoclasts with TUNEL-positive nuclei and caspase-3-immunolabeled osteoclasts were found. A significant reduction in the number of TRAP-positive osteoclasts and a high frequency of apoptotic osteoclasts were observed in CimG. Under TEM, detached osteoclasts from the bone surface showed typical features of apoptosis. Moreover, a significant reduction in the numerical density of RANKL-positive cells was observed in CimG. The significant reduction in the number of osteoclasts may be due to cimetidine-induced osteoclast apoptosis. However, RANKL immunoexpression reduction also suggests a possible interference of cimetidine treatment in the osteoclastogenesis.
authors.affiliation: Federal University of São Paulo, Department of Morphology and Genetics, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Longhini
authors.forename: Priscila Aparecida
authors.initials: PA
authors.lastname: de Oliveira
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Souza Faloni
authors.forename: Estela
authors.initials: E
authors.lastname: Sasso-Cerri
authors.forename: Paulo Sérgio
authors.initials: PS
authors.lastname: Cerri
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D046529:Microscopy, Electron, Transmission; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010519:Periodontium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand / Q000378:metabolism*; D051381:Rats
chemical_list: D006635:Histamine H2 Antagonists; D053245:RANK Ligand; D002927:Cimetidine