دورية أكاديمية
Macrophage Polarization and Alveolar Bone Healing Outcome: Despite a Significant M2 Polarizing Effect, VIP and PACAP Treatments Present a Minor Impact in Alveolar Bone Healing in Homeostatic Conditions.
| العنوان: | Macrophage Polarization and Alveolar Bone Healing Outcome: Despite a Significant M2 Polarizing Effect, VIP and PACAP Treatments Present a Minor Impact in Alveolar Bone Healing in Homeostatic Conditions. |
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| المؤلفون: | Azevedo MCS; Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Bauru, Brazil., Fonseca AC; Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Bauru, Brazil., Colavite PM; Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Bauru, Brazil., Melchiades JL; Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Bauru, Brazil., Tabanez AP; Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Bauru, Brazil., Codo AC; School of Pharmaceutical Sciences, Department of Immunology, São Paulo State University, Araraquara, Brazil., de Medeiros AI; School of Pharmaceutical Sciences, Department of Immunology, São Paulo State University, Araraquara, Brazil., Trombone APF; Department of Health Sciences, Centro Universitário Sagrado Coração (UNISAGRADO), Bauru, Brazil., Garlet GP; Bauru School of Dentistry, Department of Biological Sciences, University of São Paulo, Bauru, Brazil. |
| المصدر: | Frontiers in immunology [Front Immunol] 2021 Dec 21; Vol. 12, pp. 782566. Date of Electronic Publication: 2021 Dec 21 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Alveolar Process/*injuries , Macrophage Activation/*drug effects , Pituitary Adenylate Cyclase-Activating Polypeptide/*administration & dosage , Vasoactive Intestinal Peptide/*administration & dosage , Wound Healing/*immunology, Alveolar Process/drug effects ; Alveolar Process/immunology ; Alveolar Process/surgery ; Animals ; Cell Differentiation/drug effects ; Cell Differentiation/immunology ; Disease Models, Animal ; Female ; Immunomodulation/drug effects ; Male ; Mice ; Osteoblasts/physiology ; Osteogenesis/drug effects ; Osteogenesis/immunology ; Tooth Extraction/adverse effects ; Wound Healing/drug effects ; X-Ray Microtomography |
| مستخلص: | Host inflammatory immune response comprises an essential element of the bone healing process, where M2 polarization allegedly contributes to a favorable healing outcome. In this context, immunoregulatory molecules that modulate host response, including macrophage polarization, are considered potential targets for improving bone healing. This study aims to evaluate the role of the immunoregulatory molecules VIP (Vasoactive intestinal peptide) and PACAP (Pituitary adenylate cyclase activating polypeptide), which was previously described to favor the development of the M2 phenotype, in the process of alveolar bone healing in C57Bl/6 (WT) mice. Experimental groups were submitted to tooth extraction and maintained under control conditions or treated with VIP or PACAP were evaluated by microtomographic (µCT), histomorphometric, immunohistochemical, and molecular analysis at 0, 3, 7, and 14 days to quantify tissue healing and host response indicators at the healing site. Gene expression analysis demonstrates the effectiveness of VIP or PACAP in modulating host response, evidenced by the early dominance of an M2-type response, which was paralleled by a significant increase in M2 (CD206 + ) in treated groups. However, despite the marked effect of M1/M2 balance in the healing sites, the histomorphometric analysis does not reveal an equivalent/corresponding modulation of the healing process. µCT reveals a slight increase in bone matrix volume and the trabecular thickness number in the PACAP group, while histomorphometric analyzes reveal a slight increase in the VIP group, both at a 14-d time-point; despite the increased expression of osteogenic factors, osteoblastic differentiation, activity, and maturation markers in both VIP and PACAP groups. Interestingly, a lower number of VIP and PACAP immunolabeled cells were observed in the treated groups, suggesting a reduction in endogenous production. In conclusion, while both VIP and PACAP treatments presented a significant immunomodulatory effect with potential for increased healing, no major changes were observed in bone healing outcome, suggesting that the signals required for bone healing under homeostatic conditions are already optimal, and additional signals do not improve an already optimal process. Further studies are required to elucidate the role of macrophage polarization in the bone healing process. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Azevedo, Fonseca, Colavite, Melchiades, Tabanez, Codo, de Medeiros, Trombone and Garlet.) |
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| فهرسة مساهمة: | Keywords: M2 macrophages; PACAP; VIP; bone healing; osteoimmunology |
| المشرفين على المادة: | 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) 37221-79-7 (Vasoactive Intestinal Peptide) |
| تواريخ الأحداث: | Date Created: 20220107 Date Completed: 20220214 Latest Revision: 20231105 |
| رمز التحديث: | 20231105 |
| مُعرف محوري في PubMed: | PMC8724033 |
| DOI: | 10.3389/fimmu.2021.782566 |
| PMID: | 34992601 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.782566 |