Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars

Longhini, Renata; Aparecida de Oliveira, Priscila; Sasso‐Cerri, Estela; Cerri, Paulo Sérgio

doi:10.1902/jop.2013.130453

Cited by 35Oral microbiology and periodontitis researchBone Metabolism and DiseasesPeriodontal Regeneration and Treatments

Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars

Longhini, Renata, Aparecida de Oliveira, Priscila, Sasso‐Cerri, Estela, Cerri, Paulo Sérgio·2014·Journal of Periodontology

DOI 10.1902/jop.2013.130453

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Abstract

Background: There is evidence that histamine released during inflammation plays a role in bone metabolism via the H 2 receptor, stimulating bone resorption. The purpose of this study is to evaluate whether cimetidine, a histamine H 2‐receptor antagonist, interferes with the initiation and progression of induced periodontal disease in rat molars. Methods: Forty male rats received 100 mg/kg body weight of cimetidine (cimetidine group [CimG]) or saline solution (sham group [SG]). Periodontal disease was induced in the maxillary left first molars (PDSG and PDCimG); maxillary right molars were used as non‐ligature controls. After 7, 15, 30, and 50 days, maxillary fragments were embedded in paraffin. The sections were stained with Masson trichrome and hematoxylin and eosin and subjected to the tartrate‐resistant acid phosphatase (TRAP) method. The distances between the cemento‐enamel junction (CEJ) and alveolar process (AP) crest, as well as between the CEJ and junctional epithelium (JE) level, were measured; the number of inflammatory cells was computed. Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) immunohistochemistry was carried out, and the RANKL/OPG ratio was calculated. Results: In PDSG and PDCimG, a significant increase (P ≤0.05) was observed in CEJ‐AP and CEJ‐JE distances. However, the increases in both distances were significantly less in PDCimG compared with PDSG at 15, 30, and 50 days. Numerous TRAP‐positive osteoclasts were found in the PDSG and PDCimG. In PDCimG, the volume density of inflammatory cells and the RANKL/OPG ratio were significantly lower (P ≤0.05) than in PDSG. Conclusions: Cimetidine exerts a beneficial effect on periodontal disease in rats, decreasing the RANKL/OPG ratio in gingival connective tissue and reducing alveolar bone resorption.

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The RANKL/RANK/OPG system is a key mediator of osteoclastogenesis.
“Thus, the RANKL/RANK/OPG system is a key mediator of osteoclastogenesis [19, 86, 89].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [89]
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 [89]

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Cimetidine reduces RANKL/OPG ratio and IL-6 immunoexpression in the gingival lamina propria of rat molars with induced periodontal disease
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Authors: Longhini, R., Aparecida de Oliveira, P., Sasso‐Cerri, E., & Cerri, P. S.
Affiliations: Universidade Federal de São Paulo (BR)
Universidade Estadual Paulista (Unesp) (BR)
Corresponding author: Cerri, Paulo Sérgio
ORCID: Longhini, Renata
Sasso‐Cerri, Estela
Cerri, Paulo Sérgio
Venue: Journal of Periodontology
Publisher: Wiley
Published: 2014-08
Volume: 85
Issue: 8
Pages: 1115-1125
ISSN: 0022-3492 (ISSN-L)
1943-3670
DOI: 10.1902/jop.2013.130453
OpenAlex: W2054430832
Cited by: 35
References: 53
Citations by year: 2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 1
FWCI: 3.65
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Periodontology (publishedVersion)
PubMed (publishedVersion)
Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) (submittedVersion)
UNESP Institutional Repository (São Paulo State University) (submittedVersion)
UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo ((FAPESP‐2010/10391‐9, 2010/03571‐0, 2007/59374‐6))
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Topics: Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords: cimetidine, alveolar bone loss, periodontitis, ligature-induced periodontitis, histamine H2 receptor antagonism, bone resorption, RANKL/OPG ratio, osteoclasts, gingivitis, rat molars
MeSH terms: Tartrate-Resistant Acid Phosphatase, Acid Phosphatase, Alveolar Process, Animals, Cimetidine, Connective Tissue, Disease Models, Animal, Coloring Agents, Epithelial Attachment, Fibroblasts, Gingiva, Histamine H2 Antagonists, Isoenzymes, Male, Maxilla, Molar, Periodontitis, Time Factors, Alveolar Bone Loss, Rats, Sprague-Dawley, Disease Progression, Tooth Cervix, Rats, Osteoprotegerin, RANK Ligand

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Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars

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