Increased apoptosis in osteoclasts and decreased RANKL immunoexpression in periodontium of cimetidine-treated rats

Increased apoptosis in osteoclasts and decreased RANKL immunoexpression in periodontium of cimetidine-treated rats

Author Longhini, Renata Autor UNIFESP Google Scholar
Oliveira, Priscila Aparecida de Autor UNIFESP Google Scholar
Souza Faloni, Ana Paula de Autor UNIFESP Google Scholar
Sasso-Cerri, Estela Autor UNIFESP Google Scholar
Cerri, Paulo Sergio Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Estadual Paulista
Abstract It has been demonstrated that histamine interferes with the recruitment, formation and activity of osteoclasts via H1- and H2-receptors. Cimetidine is a H2-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 ?B 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.
Keywords alveolar bone
apoptosis
cimetidine
osteoclast
osteoclastogenesis
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: FAPESP - 2007/59374-6
FAPESP: 2010/03571-0
FAPESP: 2010/10391-9
Date 2013-02-01
Published in Journal of Anatomy. Hoboken: Wiley-Blackwell, v. 222, n. 2, p. 239-247, 2013.
ISSN 0021-8782 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 239-247
Origin http://dx.doi.org/10.1111/joa.12011
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000313806100009
URI http://repositorio.unifesp.br/handle/11600/35894

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