Salivary molecules of bone remodeling and tissue repair after head and neck radiotherapy.

Head and neck radiotherapy causes quantitative and qualitative changes in saliva. The objective of this case-control study was to evaluate the salivary biomarkers associated with bone remodeling and tissue repair in patients submitted to radiotherapy for head and neck cancer treatment, compared with non-irradiated individuals. Total unstimulated saliva was collected for ELISA assay analysis of receptor activator for nuclear factor κ B (RANK) and its ligand (RANK-L), osteoprotegerin, matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2, vascular endothelial growth factor, and epidermal growth factor. Statistics were performed, and revealed that salivary RANK (p = 0.0304), RANK-L (p = 0.0005), matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2 (p = 0.0067), vascular endothelial growth factor (p = 0.0060), and epidermal growth factor (p < 0.0001) were reduced in patients, compared with the control group. Osteoprotegerin did not differ between the groups (p = 0.3765). Salivary biomarkers did not differ according to radiotherapy completion time (p > 0.05). In conclusion, the lower output of the salivary molecules - essential for bone remodeling and tissue repair - may disrupt tissue homeostasis and play a role in the pathogenesis of the radiotherapy-induced deleterious effects in the oral cavity.

Salivary molecules of bone remodeling and tissue repair after head and neck radiotherapy

Abstract Head and neck radiotherapy causes quantitative and qualitative changes in saliva. The objective of this case-control study was to evaluate the salivary biomarkers associated with bone remodeling and tissue repair in patients submitted to radiotherapy for head and neck cancer treatment, compared with non-irradiated individuals. Total unstimulated saliva was collected for ELISA assay analysis of receptor activator for nuclear factor κ B (RANK) and its ligand (RANK-L), osteoprotegerin, matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2, vascular endothelial growth factor, and epidermal growth factor. Statistics were performed, and revealed that salivary RANK (p = 0.0304), RANK-L (p = 0.0005), matrix metalloproteinase-9/ tissue inhibitor of metalloproteinase-2 (p = 0.0067), vascular endothelial growth factor (p = 0.0060), and epidermal growth factor (p < 0.0001) were reduced in patients, compared with the control group. Osteoprotegerin did not differ between the groups (p = 0.3765). Salivary biomarkers did not differ according to radiotherapy completion time (p > 0.05). In conclusion, the lower output of the salivary molecules - essential for bone remodeling and tissue repair - may disrupt tissue homeostasis and play a role in the pathogenesis of the radiotherapy-induced deleterious effects in the oral cavity.

Revisões integrativas: conceitos, planejamento e execução / Integrative reviews: concepts, planning, and execution

Objetivo: Fornecer um guia no formato de checklist para auxiliar pesquisadores na condução de revisões integrativas em Odontologia. Métodos:O guiapara revisões integrativas em Odontologiafoi construído a partir do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (The PRISMA Statement). Resultados:Para o delineamento de revisões integrativas em Odontologia é preciso percorrer etapas distintas: 1. Identificação do tema (elaboração da pergunta de pesquisa); 2. Estabelecimento dos critérios de elegibilidade de estudos; 3. Busca sistematizada em diversas fontes de informação; 4. Coleta de dados; 5. Análise dos dados; 6. Discussão; 7. Apresentação da revisão/síntese do conhecimento. Os erros mais comuns ao realizar uma revisão integrativa estão relacionados à descrição incompleta ou não realização de etapas importantes, tais como: 1. Processo de seleção das evidências; 2. Estratégia de busca reprodutível; 3. Detalhes relacionados à busca, seleção e inclusão de estudos; 4. Aplicação dos critérios de elegibilidade; 5. Processo de extração dos dados (definição clara dos dados a serem extraídos, número de revisores envolvidos); 6. Apresentação do processo de seleção de estudos no formato de fluxograma; 7. Avaliação da qualidade dos estudos; 8. Síntese dos resultados. Conclusão:O guia para revisões integrativas em Odontologia apresenta utilidade na redução de equívocos metodológicos frequentemente observados nesse desenho de estudo, bem como estimula a condução de trabalhos com delineamentos robustos.

Aim: To provide a checklist to assist researchers in conducting integrative reviews in Dentistry. Methods: This guideline for integrative reviews in Dentistry was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (The PRISMA Statement). Results: Planning integrative reviews in Dentistry involves different stages: 1. Identification of the theme (elaboration of the research question); 2. Establishment of eligibility criteria; 3. Systematized search in several databases and other data sources; 4. Data collection; 5. Data analysis; 6. Discussion; 7. Report on the review/summary of findings. The most common errors when conducting an integrative review are related to incomplete description or failure to perform important steps, such as: 1. Evidence synthesis; 2. A reproducible search strategy; 3. Details related to studies' search, screening, selection; 4. Clear state eligibility criteria; 5. Data extraction process (clear definition of the data to be extracted, number of reviewers involved); 6. Presentation studies' screening and selection process in a flowchart format; 7. Evaluation of the quality of the studies; 8. Summary of the findings. Conclusion:A guideline for integrative reviews in Dentistry intends to reduce methodological issues frequently observed in this study design, as well as to encourage researchers to conduct studies with a robust design.

Contribution of atypical chemokine receptor 2/ackr2 in bone remodeling.

INTRODUCTION: Bone remodeling is a tightly regulated process influenced by chemokines. ACKR2 is a decoy receptor for CC chemokines functioning as regulator of inflammatory response. In this study we investigated whether the absence of ACKR2 would affect bone phenotype and remodeling induced by mechanical loading. METHODS: An orthodontic appliance was placed between incisors and first molar of ACKR2 deficient (ACKR2-/-) and C57BL6/J (wild-type/WT) mice. Microtomography, histology and qPCR were performed to evaluate bone parameters, orthodontic tooth movement (OTM), bone cells counts and the expression of ACKR2, bone remodeling markers, CC chemokines and chemokines receptors. Bone marrow cells (BMC) from WT and ACKR2-/- mice were differentiated in osteoclasts and osteoblasts for analysis of activity and expression of specific markers. RESULTS: Mechanical stimulus induced ACKR2 production in periodontium. The expression of ACKR2 in vitro was mostly detected in mature osteoclasts and early-differentiated osteoblasts. Although ACKR2-/- mice exhibited regular phenotype in maxillary bone, the amount of OTM, osteoclasts counts and the expression of pro-resorptive markers were increased in this group. In contrast, the number of osteoblasts and related markers were decreased. OTM resulted in augmented expression of CC chemokines and receptors CCR5 and CCR1 in periodontium, which was higher in ACKR2-/- than WT mice. In vitro experiments demonstrated an augmented formation of osteoclasts and diminished differentiation of osteoblasts in ACKR2-/- mice. CONCLUSIONS: These data suggests that ACKR2 functions as a regulator of mechanically-induced bone remodeling by affecting the differentiation and activity of bone cells and the availability of CC chemokines at periodontal microenvironment. Therapeutic strategies based on increase of ACKR2 might be useful to hinder bone loss in inflammatory conditions.