Hypertension modifies OPG, RANK, and RANKL expression during the dental socket bone healing process in spontaneously hypertensive rats



The aim of this study was to evaluate the dental socket bone healing process by histomorphometric and immunohistochemical analysis of osteoprotegerin (OPG), receptor activator of nuclear factor-κβ (RANK), and receptor activator of nuclear factor-κβ ligand (RANKL) proteins in spontaneously hypertensive rats (SHR).

Materials and methods

Under general anesthesia, 25 Wistar rats and 25 SHRs underwent upper right incisor extraction. Rats were euthanized after 7, 14, 21, 28, or 42 days of dental extractions. Histomorphometric and immunohistochemical analyses of OPG, RANK, and RANKL proteins were performed.


Histomorphometric results showed decreased bone healing and reduced bone trabecular thickness in SHRs. Immunohistochemical reactions showed intense RANKL and RANK immunolabeling at 14 and 28 postoperative days and mild OPG immunolabeling at 7, 14, and 21 days after surgery in SHRs.


The results of this study show that RANK, RANKL, and OPG immunolabeling was altered in SHRs, and these results are associated with bone healing delay and decreased trabecular thickness in SHRs.

Clinical relevance

Hypertension alters the expression of RANK, RANKL, and OPG and delays the socket bone healing process. These alterations could influence some dental procedures such as orthodontic treatment and implant placement.

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The authors would like to thank the Department of Pathology and Clinical Propedeutics of the School of Dentistry of Araçatuba, UNESP, for allowing the use of the equipment for histomorphometric analysis. This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, 2008/01893-0) and UNESP Research Internationalization Program (PROINTER/PROPe—UNESP).

Conflict of interest

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). Natalia Manrique received a fellowship from FAPESP (2008/01893-0). The authors declared that no competing interests exist and they approved the submission of the manuscript.

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Correspondence to Natalia Manrique.

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Manrique, N., Pereira, C.C.S., Luvizuto, E.R. et al. Hypertension modifies OPG, RANK, and RANKL expression during the dental socket bone healing process in spontaneously hypertensive rats. Clin Oral Invest 19, 1319–1327 (2015). https://doi.org/10.1007/s00784-014-1369-0

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  • Extraction socket healing
  • Histomorphometry
  • Spontaneously hypertensive rats
  • OPG
  • RANK