Hydrogel/AnxA12-26 modulates wound healing, proliferation and cell apoptosis in mPDL lines

Introduction: Diabetes mellitus (DM) is a metabolic disease of inflammatory nature, characterized by hyperglycemia and activation of the immune response. In the oral cavity, DM is a risk factor for periodontal disease and delayed wound healing. Patients with DM have an increased possibility of developing periodontitis compared to individuals with normal glycemic level. These diseases are related to the immune response, characterized by increased levels of inflammatory mediators and excessive and prolonged immune-inflammatory responses. Recent studies from our research group show that the protein Annexin A1 (peptide AnxA12-26) is related to the regulation of apoptosis, vascularization, cell differentiation and inflammation. AnxA1 is a protein that binds to the phospholipid membrane in a calcium-dependent manner and has its anti-inflammatory properties regulated by glucocorticoids, promoting the resolution of inflammatory processes. In this context, we highlight the mimetic peptide AnxA12-26, consisting of the first 26 amino acids of AnxA1 that reproduces its biological functions (which is why the peptide is used in studies of acute, chronic and systemic inflammation). With these considerations, a better understanding of how diabetes influences healing processes is crucial for the prevention and treatment of oral complications. Objective: To evaluate the effect of AnxA12-26 as an anti-inflammatory/scarring product in mPDL (mouse periodontal ligament fibroblast) cells after induction with lipopolysaccharide (LPS) and/or high glucose concentration. Methodology: mPDL cells, induced or not with LPS and/or glucose were cultured and treated with the hydrogel containing the peptide AnxA12-26, incorporated in anionic carboxymethylcellulose gel (2µM, 15µM and 100µM), for 24, 48 and 72 hours, for cellular analysis related to wound healing, proliferation, viability, cell apoptosis and DNA damage. Results: Our results show that periodontal ligament cells, when treated with hydrogel/AnxA12-26, exhibit decreased proliferation, increased wound healing and cell apoptosis by inducing DNA damage. Differently, we did not observe changes in cell morphology or viability. These data show that in this inflammation model the molecular mechanisms induced by hydrogel/AnxA12-26 lead to the regulation of antiproliferative, apoptotic and inflammatory pathways. Conclusion: Taken together, the data obtained contribute to the clarification of ANXA1’s mechanisms of action in the process involving periodontal repair and, in addition, increase the possibilities of new, cost-effective therapeutic approaches for the treatment of these chronic inflammatory conditions.