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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Gene expression analysis of cytokines and MMPs in melatonin and rhBMP-2 enhanced bone remodeling
Marina Ribeiro Paulini, Letícia Ferreira Montarele, Dimitrius Leonardo Pitol, Gisele Giannocco, Bruno Fiorelini Pereira, Daniela Vieira Buchaim, Carlos Henrique Bertoni Reis, Rogério Leone Buchaim, Joao Paulo Mardegan Issa
Marina Ribeiro Paulini, Letícia Ferreira Montarele, Dimitrius Leonardo Pitol, Department of Basic and Oral Biology, University of São Paulo, Ribeirao Preto 14040-904, Brazil
Gisele Giannocco, Bruno Fiorelini Pereira, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Federal University of São Paulo, Diadema 09972-270, Brazil
Daniela Vieira Buchaim, Medical School, University Center of Adamantina, Adamantina 17800-000, Brazil
Daniela Vieira Buchaim, Carlos Henrique Bertoni Reis, Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia, Marilia 17525-902, Brazil
Rogério Leone Buchaim, Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru 17012-901, Brazil
Joao Paulo Mardegan Issa, Department of Basic and Oral Biology, Ribeirão Preto School of Dentistry, University of São Paulo, Ribeirao Preto 14040-904, Brazil
Author contributions: Paulini MR participated in conceptualization, writing-original draft preparation, writing-review and editing, and visualization of the study; Montarele LF participated in conceptualization; Pitol DL participated in validation, investigation and data curation; Giannocco G participated in methodology and formal analysis; Pereira BF participated in methodology, validation and formal analysis; Buchaim DV participated in data curation and visualization; Reis CHB participated in validation and formal analysis; Buchaim RL participated in formal analysis, investigation and data curation, writing-original draft preparation, writing-review and editing, visualization and supervision; Issa JPM participated in writing-review and editing and supervision.
Supported by FAPESP, No. 2019/03699-1.
Institutional animal care and use committee statement: The methodology presented here was evaluated and approved by the Animal Experimentation Ethics Committee of FORP-USP, with process number 2017.1.294.58.4.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The data presented in this study are available on request from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Joao Paulo Mardegan Issa, PhD, Professor, Department of Basic and Oral Biology, Ribeirão Preto School of Dentistry, University of São Paulo, Ave Cafe S-N, Ribeirao Preto 14040-904, Brazil.
jpmissa@forp.usp.br
Received: May 13, 2024
Revised: August 3, 2024
Accepted: August 26, 2024
Published online: November 18, 2024
Processing time: 185 Days and 15.9 Hours
BACKGROUND
In the medical and dental fields, there is a need for studies of new therapeutic approaches for the treatment of bone defects that cause extensive bone loss. Melatonin may be an important endogenous biological factor for bone remodeling, and growth factors may enhance the repair process.
AIM
To evaluate the gene expression of cytokines (IL-1β, IL-6, IL-10 and TNF-α), markers of osteoclastogenesis (RANK, RANKL and OPG) and MMPs (MMP-1, MMP-2, MMP-8 and MMP-13) from the treatment of melatonin associated with an osteogenic membrane and rhBMP-2 on the recovery of a bone injury.
METHODS
Sixty-four rats were used and divided into 9 experimental groups and were formed according to the treatment carried out in the region of the bone lesion, which varied between the combination of 1, 10 and 100 μmol/L of melatonin. Gene Expression analysis was performed using real time-PCR by reading the concentration of total RNA and reverse transcription.
RESULTS
There were differences between groups when compared with clot or scaffold control, and improvement with a higher concentration of melatonin or rhBMP-2. The combination melatonin (1 µg) with 5 μg of rhBMP-2, using the guided bone regeneration technique, demonstrated some effects, albeit mild, on bone repair of critical bone defects.
CONCLUSION
This indicates that the approach for administering these substances needs to be reassessed, with the goal of ensuring their direct application to the affected area. Therefore, future research must be carried out, seeking to produce materials with these ideal characteristics.
Core Tip: Melatonin is believed to be an important endogenous biological factor for bone remodeling. Furthermore, growth factors such as bone morphogenetic proteins (rhBMPs) have been used to repair bone defects. The aim of this study was to assess the expression of cytokine genes (IL-1β, IL-6, IL-10 and TNF-α), markers of osteoclastogenesis (RANK, RANKL and OPG) and MMPs (MMP-1, MMP-2, MMP-8 and MMP-13) from the treatment of melatonin associated with an osteogenic membrane and rhBMP-2 on the recovery of a bone injury.
