Increased apoptosis in osteoclasts and decreased RANKL immunoexpression in periodontium of cimetidine‐treated rats
Open accessAbstract
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 RANK L (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.
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RANKL is also produced by stromal cells, osteoblasts, and fibroblasts.
“There is evidence that osteocytes act as the main source of RANKL to promote osteoclastogenesis [167, 168], although this factor has also been demonstrated to be produced by other cell types such as stromal cells [194], osteoblasts, and fibroblasts [88, 89].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [88]
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- Authors
- Longhini, R., de Oliveira, P. A., de Souza Faloni, A. P., Sasso‐Cerri, E., & Cerri, P. S.
- Affiliations
- Universidade Federal de São Paulo (BR)
- Federal University of São Paulo (UNIFESP) Department of Morphology and Genetics São Paulo SP Brazil
- Universidade Estadual Paulista (Unesp) (BR)
- Corresponding author
- Cerri, Paulo Sérgio
- Venue
- Journal of Anatomy
- Publisher
- Wiley
- Published
- 2012-12-02
- Volume
- 222
- Issue
- 2
- Pages
- 239-247
- ISSN
- 0021-8782 (ISSN-L)
- 1469-7580
- PMC
- PMC3632229
- OpenAlex
- W2095240392
- Cited by
- 23
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 1
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Anatomy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) (submittedVersion)
- Americanae (AECID Library) (submittedVersion)
- UNESP Institutional Repository (São Paulo State University) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2007/59374-6, 2010/03571-0, 2010/10391-9)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- cimetidine, osteoclast apoptosis, RANKL, osteoclastogenesis, alveolar bone, periodontium, histamine H2 receptor antagonism, caspase-3, bone resorption, histamine
- MeSH terms
- Animals, Cimetidine, Histamine H2 Antagonists, Immunohistochemistry, Male, Osteoclasts, Periodontium, Apoptosis, In Situ Nick-End Labeling, Microscopy, Electron, Transmission, Rats, RANK Ligand
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