The Role of Apoptotic Factors in Assessing Progression of Periodontal Disease

Abstract

BackgroundThe mechanisms responsible for periodontal disease progression remain unclear. However, recent studies suggest that apoptosis may be one mechanism underlying the pathophysiology of periodontal disease progression. This pilot study is the 3 month follow-up of our published baseline study on the presence of apoptotic factors in serum, saliva, and gingival crevicular fluid (GCF) and their association with periodontal disease severity and activity.MethodsGCF samples were obtained from 37 adult patients with chronic periodontitis (CP) and 7 healthy controls. Clinical measurements, including probing depth (PD), clinical attachment level (CAL), and radiographs, were used to evaluate data by sites and to classify patients into healthy, mild, and moderate/severe CP groups. Enzyme-linked immunosorbent assays were used to measure apoptosis or DNA fragmentation levels in GCF. Western immunoblotting was used to detect several apoptotic proteins, Fas, FasL, sFasL, and caspase-3 expression and its cleavage products in GCF.ResultsAt the patient level clinical and apoptotic measurements change minimally over time. At the site level, DNA fragmentation levels increase with increasing PDs at 3 months and baseline. Apoptotic protein expression exhibits increasing trends with increasing PDs at baseline and 3 months. FasL and Active FasL show a high specificity and PPV; low sensitivity and NPV. Caspase-3 products (ProCas35K and Active Cas) show a high PPV with moderate to high specificity; low sensitivity and NPV. ProCas70K shows a high PPV with moderate to high sensitivity; low specificity and NPV.ConclusionFactors associated with apoptosis show minimal changes in expression in periodontitis groups in comparison to a healthy group over a short time interval (3 months). However, at the site level, apoptotic factors (DNA fragmentation and apoptotic proteins) exhibit significant increases or increasing trends with increasing PDs at any time point examined (baseline or 3 months). Several of these apoptotic factors also exhibit a high sensitivity and high positive predictive value. Thus, apoptotic molecules may be helpful biomarkers of disease status at any point in time.

Analysis of the Annexin v Apoptosis Marker Level and Dental Status in Patients With Chronic Generalized Perodontitis and Bronchoectatic Disease

“…Исходя из поставленной нами цели было обследовано 130 человек, разделенных на 3 группы (табл. [5,9]. Отличия были статистически значимы при значении p<0,05.…”

“…Доказано, что возникновение и прогрессирование генерализованного пародонтита во многом обусловлены нарушением регуляторных механизмов клеточной пролиферации, дифференцировки и апоптоза в слизистой оболочке десны под воздействием многочисленных факторов агрессии [3][4][5].…”

Necroptosis has a crucial role in the development of chronic periodontitis

“…The processes responsible for the progression of periodontal disease remain uncertain 10 . Cell death, traditionally thought to be the consequence of inflammation, has now been linked to the etiology of inflammatory disorders.…”

“…Apoptosis is a critical regulator of the host immune system that is affected by cytokines, bacterial and viral infections, immune cells themselves, and the extracellular matrix. 10 Unlike apoptosis, necrosis is an uncontrolled process characterized by a rapid loss of membrane integrity, release of extracellular contents, severe inflammation, and immune system activation. 12 …”

“…According to prior studies, many apoptotic agents have a high sensitivity and positive prediction capability for periodontal disease. 10 Several investigations have indicated that inflamed periodontal tissue has a lower apoptosis rate. 17 , 18 Recent trials indicated that RIPK3 and MLKL-mediated necroptotic cell death played a role in the development of periodontitis.…”