lab meeting presentation
Transcript: Sandeep Kumar oral biology university of Leeds Supervisors: Dr E L Mostafa Dr Jinous Tahmassebi Dr Farideh Javid Identification of the abilities of Cannabinoids to address deterrent inflammation during periodontitis and their role during periodontal tissue regeneration. Title Sandeep Kumar PhD Second Year Supervisors: Dr EL Mostafa Raif Dr Jinous Tahmassebi Dr Farideh Javid introduction commonly found disease, incidence depends on age, sex and socioeconomic conditions.Indirect costs due to oral conditions worldwide amounted to US$144 billion yearly. Journal of Dental Research 2017, Vol. 96(4) 380–387 Periodontium and Periodontitis Gradual inflammation of periodontal tissues i.e. periodontitis leads to loss of bone, eventually loss of function Implications of periodontal diseases J Can Dent Assoc 2000; 66:594-7 environmental perturbations in the periodontal tissues 1. trauma 2. idiopathic growth of a keystone pathogen 3. host is genetically susceptible pathogens elicit inflammation changes the nutrient foundation of the ecological niche (i.e. periodontal pocket). The altered nutrient foundation promotes the proportional expansion of pathobionts relative to symbionts, promoting inflammation that ultimately leads to connective tissue and bone destruction. ETIOLOGY:PERIODONTITIS periodontitis oral hygiene maintenance local drug delivery -- antibiotics systemic antibiotics surgical approaches anti-inflammatory modulation NEWER APPROACHES TO ADDRESS PERIODONTITIS Li Dehao et al. 2017 Cannabidiol(CBD) administration reduces sublesional cancellous bone loss in rats with severe spinal cord injury Fabisiak A et al. 2017 Cannabinoids as gastrointestinal anti-inflammatory drugs. Li et al. 2013 Anti-Inflammatory Role of Cannabidiol (CBD) and O-1602 in Cerulein-Induced Acute Pancreatitis in Mice Ribeiro A et al. 2012 Cannabidiol(CBD), a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury AIM canabinoids: 1. acts as anti-inflammatory agents 2. acts in preventing bone resorption 3. got receptors in human body 4. acts on endocannabinoid system Periodontitis : 1. Is a inflammatory disease 2. causes bone resorption 3. canabinoid receptors are found in periodontal ligament Review To evaluate the ability of cannabinoids to address the chronic periodontal diseases. objectives 1. To investigate the anti-inflammatory effects of cannabinoids. 2. To assess the effect of cannabinoids on osteogenesis. 3. To assess the effect of canabinoids on osteoclastogenesis. Recently it is also found that the endocannabinoid system does not just respond to the endocannabinoids produced in the body, but also respond to external cannabinoids like the phytocannabinoid cannabidiol, or CBD. Marcelo H. Napimoga et al. 2014- used CBD and showed anti-inflammatory effects -------- experimental periodontitis in rats CANNABINOIDS IN PERIODONTITIS Abidi A A et al. 2018 targeted the endocannabinoid system, showed it could offer a new therapeutic approach for treating chronic inflammation in periodontal disease. Niyogi et al 2019 showed canabinoids have antibacterial property against periodontal pathogens IN-VITRO model LPS/Flagellin ------ TIG-K cells/ periodontal cells --- inflammatory response, at m-RNA level and protein level Interleukin-8 (IL-8) plays vital role in pathogenesis of periodontal diseases. inflammatory pathway involved confirmation of pathway using knockdown and gene silencing Results Key Results TIG- K (GINGIVAL KERATINOCYTES): OBSERSEVED EXPRESSION cytotoxicity (LPS, Flagellin and Canabinoids ) il-8 transcription at 3 hours il-8 translation at 3 hours il-8 translation at 24 hours Analysis Results replicated using Periodontal cells from various donors and also with CBG( canabegerol) AEA (Anandamide)/2AG (2-Arachidonoylglycerol) CBD (Canabidiol)/ CBG ( Canabegerol) Subtopic 1 cell viability TIG-K viability with test drug CBD CBG, AM-251- slective antagonist CB1 O-1602 - Non- Selective Antagonist AM-630- Selective antagonist CB2 Subtopic 2 Transcription analysis 1 uM Subtopic 3 Translation AT 3 HOURS AT 24 HOURS 1 uM 1 uM Conclusion Conclusion Pre-treatment with CBD markedly attenuates the expression of IL-8 stimulated TIG-K/periodontal cells with obnoxious stimulus flagellin. This non-psychotropic cannabis product (CBD) may therefore play a vital role in addressing chronic periodontal problems. What’s next What’s next To identify other inflammatory cytokines like IL-6, IL-1b and TNF-α at mRNA and protein levels Genes regulating the mineralization i.e. RANK/RANKL and OPG will be studied. Identify their role in bone mineralization and demineralisation during Periodontitis. Thank you Thank you REFERENCES REFERENCES
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