Evaluation of apoptosis and hypoxia‐related factors in gingival tissues of smoker and non‐smoker periodontitis patients

Abstract

Objective: Smoking causes pathological changes in all tissues, including gingiva and alveolar bone. The aim of present study was to evaluate apoptotic tissue alterations and tissue destruction in smoker and non-smoker periodontitis patients and healthy individuals. Methods: Gingival biopsy samples from 15 systemically and orally healthy individuals (Group 1), 15 systemically healthy periodontitis patients (Group 2), 15 systemically and orally healthy smokers (Group 3), and 15 systemically healthy smoker periodontitis patients (Group 4) were enrolled in the present study. Clinical periodontal measurements as plaque index (PI), gingival index (GI), and clinical attachment levels (CAL) were recorded, and gingival biopsies were obtained. Biopsy samples were fixed in formalin solution and embedded in paraffin. Fibroblast and inflammatory cell counts were determined via histomorphometrically. Hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor(VEGF), tissue inhibitor of matrix metalloproteinase-1(TIMP-1), matrix metalloproteinases-8(MMP-8) expressions, Bax, Bcl-2, and caspase-3 expressions were evaluated via immunohistochemistry.Results: Demographic data of the study groups were similar. Smoking levels of the smokers were also similar. The highest fibroblast cell counts were observed in healthy controls and the counts were similar in other groups. The highest inflammatory cell counts were found in smoker periodontitis group, and the lowest counts were found in healthy control groups. The differences were statistically significant. HIF-1α and Bax expressions were elevated and Bcl-2 decreased in smoker periodontitis patients compared with healthy individuals. However, there were no differences in VEGF, MMP-8, and TIMP-1 expressions. Conclusion:Within limits of present study, it can be suggested that both smoking and periodontitis caused similar decrease in fibroblast counts while causing a dramatic increase in inflammatory cell counts. Increased apoptosis and hypoxia also accompanied to the increased inflammation. K E Y W O R D S apoptosis, hypoxia, smoking | 393 KARATAS eT Al.

Hypoxia stimulates collagen hydroxylation in gingival fibroblasts and periodontal ligament cells

“…For instance, the vasoconstrictive effects of nicotine have been reported to create a constant state of hypoxia in the periodontal tissue of smokers and induce HIF-1α expression. 40,41 Therefore, increased PLOD2 production via HIF-1α may over-strengthen collagen and could explain why smokers have harder and more fibrous gingiva than healthy individuals. It has also been reported that cyclosporine A, an agent that causes drug-induced gingival hyperplasia, induces HIF-1α expression, 42 whereas gingival hyperplasia caused by phenytoin has been shown to reduce collagen gene expression.…”

M101, a therapeutic oxygen carrier derived fromArenicola marina, decreasedPorphyromonas gingivalis‐induced hypoxia and improved periodontal healing

“…Likewise, the role of P. gingivalis in augmenting NFκB secretion is already well‐established 18,34 . The recent focus of several studies on hypoxia and hypoxia‐correcting strategies for tissue engineering emphasizes the important role of hypoxia and its associated mediators in the underlying intricate inflammatory cascades, 35,36 especially in the context of periodontitis 37–39 . For instance, HIF‐1α has been implicated in the pathogenesis of several inflammatory diseases including periodontitis 40,41 and its upregulation in response to hypoxic microenvironment and inflammation in periodontal tissues has been previously reported as well 7,41,42 .…”

“…18,34 The recent focus of several studies on hypoxia and hypoxiacorrecting strategies for tissue engineering emphasizes the important role of hypoxia and its associated mediators in the underlying intricate inflammatory cascades, 35,36 especially in the context of periodontitis. [37][38][39] For instance, HIF-1α has been implicated in the pathogenesis of several inflammatory diseases including periodontitis 40,41 and its upregulation in response to hypoxic microenvironment and inflammation in periodontal tissues has been previously reported as well. 7,41,42 Our results demonstrated an amplification of hypoxia and inflammatory markers such as HIF-1α, MMP-9, and NFκB, establishing the link between P. gingivalis induced hypoxia and the resulting inflammation-mediated tissue degradation.…”

Leptin attenuates hypoxia‐induced apoptosis in human periodontal ligament cells via the reactive oxygen species–hypoxia‐inducible factor‐1α pathway

“…Hypoxia is a major concern in various oral pathological situations, such as periodontitis (Karatas et al, 2020), occlusal trauma (Ito et al, 2018) and orthodontic force stimulation (Krishnan & Davidovitch, 2006), and can influence a variety of physiological processes, including cellular metabolism (Wu et al, 2013), proliferation and apoptosis (Kato et al, 2016). The periodontal ligament (PDL), located between the © 2021 The Authors.…”