Journal Article

Therapeutic effects of peptide P140 in a mouse periodontitis model

Muller, Sylviane, Talamini, Laura, Aung, Kyaw Thu, Akiyama, Kentaro, Huck, Olivier, Kuboki, Takuo

2022

Overview

In our search for innovative drugs that could improve periodontal treatment outcomes, autophagy and its anomalies represent a potential target for therapeutic intervention. We sought to identify autophagy defects in murine experimental periodontitis and study the effectiveness of P140, a phosphopeptide known to bind HSPA8 and inhibit its chaperone properties, and that corrects autophagy dysfunctions in several autoimmune and inflammatory diseases. Experimental periodontitis was induced by placing silk ligature around mandibular first molars. Sick mice were treated intraperitoneally with either P140 or a control, scrambled peptide. After 10 days, mandibles were harvested and bone loss was measured by micro-CT. Immune cells infiltration was studied by histological analyses. Cytokines levels and autophagy-related markers expression were evaluated by qRT-PCR and western blotting. A comparison with non-affected mice revealed significant alterations in the autophagy processes in mandibles of diseased mice, especially in the expression of sequestosome 1/p62, Maplc3b, Atg5, Ulk1, and Lamp2. In vivo, we showed that P140 normalized the dysregulated expression of several autophagy-related genes. In addition, it diminished the infiltration of activated lymphocytes and pro-inflammatory cytokines. Unexpectedly P140 decreased the extent of bone loss affecting the furcation and alveolar areas. Our results indicate that P140, which was safe in clinical trials including hundreds of autoimmune patients with systemic lupus erythematosus, not only decreases the inflammatory effects observed in mandibular tissues of ligation-induced mice but strikingly also contributes to bone preservation. Therefore, the therapeutic peptide P140 could be repositioned as a decisive breakthrough for the future therapeutic management of periodontitis.

• Publisher: Springer International Publishing,Springer Nature B.V,Springer Verlag
• Subject: Animals / Anomalies / Autophagy / Biochemistry / Biochemistry, Molecular Biology / Biomedical and Life Sciences / Biomedicine / Bone loss / bone resorption / Cell Biology / Chronic conditions / Clinical trials / Computed tomography / Cytokines / Cytokines - genetics / Disease management / Disease Models, Animal / Gene expression / Gum disease / histology / Immune system / Immunosuppressive agents / Infiltration / Inflammatory diseases / Life Sciences / lupus erythematosus / Lymphocytes / Mandible / Mice / micro-computed tomography / Molars / Original / Original Article / Peptide Fragments - pharmacology / Peptides / Periodontitis / Periodontitis - drug therapy / Phosphopeptides / Silk / Systemic lupus erythematosus / therapeutics / Western blotting