VEGFA And IL17 Expression Reveals Their Potential Functional Crosstalk in Periodontitis Rats-A New Animal Model for Angiogenesis Study

Vascular Endothelial Growth Factor A (VEGFA) is a main player in physiological and pathological angiogenesis in cardiovascular development, organs remodeling, wound healing, cell infiltration in inflammation, tumor development and metastasis. Interleukin 17 (IL17) is pro-inflammation cytokine secreted by a variety of cell types playing an important role in progression of infection, cardiovascular disease, autoimmune disease, and diabetes. Despite the emerging reports show that VEGFA and IL17 are both involved in vasculogenetic diseases, there is an evident paucity of information about functional cross talk between these two cytokines. Here, we analyze expression pattern of VEGFA and IL17 in a new periodontitis rat model through immunohistochemistry (IHC) staining. A total of 110 jaw tissues is taken at designed time points from rats. Periodontitis is created by sticking an orthodontic square wire on the surface of the left maxillary first molar (Group A, n=35), ligating a metal wire ligature on the edge of gingival sulcus of the left mandibular first molar (Group B, n=35), or both an orthodontic square wire on the surface of the left maxillary and a ligature in the cervical of the left mandibular first molar are installed at the same time (Group C, n=35). Untreated rats periodontia (Control group, n=5) are used as normal control. Histological analysis confirms the inflammatory features developing through time in interferenced rats periodontal tissues. Pathological analysis of VEGFA and IL17 expression shows that VEGFA and IL17 positive cells increase overtime comparing to control group; VEGFA and IL17 positive polykaryon cells, pericytes and endothelial cells are found around immature vessels near and/or in alveolar bones; pathological vasculature changes in group A is greater than group B overtime, whereas bone resorption in group B is greater than group A; both development of vasculature and bone resorption are parallel in group C, along with accompanying increase of both VEGFA and IL17 expression in stromal tissue, leukecytes, endothelial cells and pericytes around newly formed vessels, and osteoclast-like polykaryon cells; Extracellular IL17 expression is dominant and reaches peak at second week in group A, whereas intercellular IL17 expression is dominant in group B and reaches peak at forth week. Most interestingly, group C has dominant intercellular IL17 expression although extracellular IL17 reaches peak at second week same to group A. Removing of interferences reverses the increasing expression of VEGFA/IL17 in all three groups with milder inflammation. We conclude that a new animal model to study angiogenesis and bone destruction is well established by characterization of developing vasculature, infiltrated immune cells, periodontal ligament fiber disorder and alveolar bone destruction in this periodontitis model. The increase of VEGFA/ IL17 expression in endothelial cells and pericytes around immature vessels, as well as osteoclasts-like polykaryons in alveolar lacunas in this rat model suggests that VEGFA and IL17 are probably involved in remodeling of bone and vasculature caused by inflammation through potential functional crosstalk. Inhibition of producing of VEGFA and/or IL17 may be a potential therapeutic strategy for cardiovascular diseases, tumor bone metastasis, and other immune diseases including neurodegenerative diseases and even leukemia.