Alveolar bone healing in mice genetically selected in the maximum (AIRmax) or minimum (AIRmin) inflammatory reaction

Autor(es)

Colavite, Priscila Maria ^[1] ; Vieira, Andreia Espindola ^[2] ; Palanch Repeke, Carlos Eduardo ^[3] ; de Araujo Linhari, Rafaella Pavanelli ^[1] ; Carneiro Spera De Andrade, Raissa Gonsalves ^[1] ; Borrego, Andrea ^[4] ; De Franco, Marcelo ^[5] ; Trombone, Ana Paula Favaro ^[6] ; Garlet, Gustavo Pompermaier ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Bauru, SP - Brazil

^[2] Fed Univ Alagoas UFAL, Inst Biol & Hlth Sci ICBS, Histol & Embryol Lab, Maceio, AL - Brazil

^[3] Univ Fed Sergipe, Dept Dent, Lagarto, Sergipe - Brazil

^[4] Govt State Sao Paulo, Secretary Hlth, Butantan Inst, Immunogenet Lab, Sao Paulo, SP - Brazil

^[5] Govt State Sao Paulo, Secretary Hlth, Inst Pasteur, Diagnost Sect, Sao Paulo, SP - Brazil

^[6] Univ Sagrado Coracao, Dept Hlth Sci, Bauru, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CYTOKINE; v. 114, p. 47-60, FEB 2019.
• Citações Web of Science: 0

Resumo

The exact role of inflammatory immune response in bone healing process is still unclear, but the success of the alveolar bone healing process seems to be associated with a moderate and transitory inflammatory response, while insufficient or exacerbated responses seems to have a detrimental influence in the healing outcome. In this context, we performed a comparative analysis of mice strains genetically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response to address the influence of inflammation genes in alveolar bone healing outcome. Experimental groups comprised 8-week-old male or female AIRmax and AIRmin submitted to extraction of upper right incisor, and evaluated at 0, 3, 7, 14 and 21 days after upper incision extraction by micro-computed tomography (mu CT), histomorphometry, birefringence, immunohistochemistry and molecular (PCRArray) analysis. Overall, the results demonstrate a similar successful bone healing outcome at the endpoint was evidenced in both AIRmin and AIRmax strains. The histormophometric analysis reveal a slight but significant decrease in blood clot and inflammatory cells density, as well a delay in the bone formation in AIRmax strain in the early times, associated with a decreased expression of BMP2, BMP4, BMP7, TGFb1, RUNX2, and ALP. The evaluation of inflammatory cells nature reveals increased GR1 + cells counts in AIRmax strain at 3d, associated with increased levels of neutrophil chemoattractants such as CXCL1 and CXCL2, and its receptor CXCR1, while F4/80 + cell prevails in AIRmin strain at 7d. Also, our results demonstrate a relative predominance of M2 macrophages in AIRmin strain, associated with an increased expression of ARG1, IL10, TGFb, while Ml macrophages prevail in AIRmax, which parallel with increased IL-1B, IL-6 and TNF expression. At late repair stage, AIRmax presents evidences of increased bone remodeling, characterized by increased density of blood vessels and osteoclasts in parallel with decreased bone matrix density, as well increased levels of MMPs, osteoclastogenic and osteocyte markers. In the view of contrasting inflammatory and healing phenotypes of AIRmin and AIRmax strains in other models, the unpredicted phenotype observed suggests the existence of specific QTLs (Quantitative trait loci) responsible for the regulation `sterile' inflammation and bone healing events. Despite the similar endpoint healing, AIRmax strain delayed repair was associated with increased presence of neutrophils and Ml1 macrophages, supporting the association of M2 cells with faster bone healing. Further studies are required to clarify the elements responsible for the regulation of inflammatory events at bone healing sites, as well the determinants of bone healing outcome. (AU)

• Processo FAPESP: 13/25824-6 - Estudo do papel do gene Slc11a1 e de genótipos selecionados para mínima e máxima reatividade inflamatória no processo de processo de reparo ósseo alveolar em camundongos
• Beneficiário: Priscila Maria Colavite Machado
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/24637-3 - MSCs e M2 como determinantes da natureza construtiva ou destrutiva de microambientes inflamatórios associados ao tecido ósseo
• Beneficiário: Gustavo Pompermaier Garlet
• Modalidade de apoio: Auxílio à Pesquisa - Temático