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

Autor(es)

Longhini, Renata ^[1] ; de Oliveira, Priscila Aparecida ^[1] ; de Souza Faloni, Ana Paula ^[1] ; Sasso-Cerri, Estela ^[1] ; Cerri, Paulo Sergio ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Paulo Unifesp, Dept Morphol & Genet, Sao Paulo - Brazil

^[2] Univ Estadual Paulista, UNESP, Sch Dent, Dept Morphol, Lab Histol & Embryol, BR-14801903 Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Anatomy; v. 222, n. 2, p. 239-247, FEB 2013.
• Citações Web of Science: 12

Resumo

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. (AU)

• Processo FAPESP: 10/03571-0 - Avaliação morfométrica, imuno-histoquímica e ultraestrutural do efeito da cimetidina na evolução da periodontite induzida em molares de ratos
• Beneficiário: Renata Longhini
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 07/59374-6 - Efeito do anti-histaminico cimetidina na reabsorcao do osso alveolar de ratos.
• Beneficiário: Renata Longhini
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 10/10391-9 - Avaliação morfométrica, imuno-histoquímica e ultraestrutural do efeito da cimetidina na evolução da periodontite induzida em molares de ratos
• Beneficiário: Paulo Sergio Cerri
• Modalidade de apoio: Auxílio à Pesquisa - Regular