Effects of 5-lipoxygenase gene disruption on inflammation, osteoclastogenesis and bone resorption in polymicrobial apical periodontitis

Paula-Silva, Francisco Wanderley Garcia; Arnez, Maya Fernanda Manfrin; Petean, Igor Bassi Ferreira; Almeida-Júnior, Luciano Aparecido de; Silva, Léa Assed Bezerra da; Faccioli, Lúcia Helena

doi:10.1016/j.archoralbio.2020.104670

Cited by 19 publications

(10 citation statements)

References 56 publications

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“…The use of colchicine, has also shown to have important effects vs. gingival inflammation, apoptosis, and alveolar bone loss (Aral et al, 2018 ). A similar finding was found for 5-lipoxygenase therapy in polymicrobial apical periodontitis (Paula-Silva et al, 2020 ), and in an experimental model for rosuvastatin therapy (Kırzıoğlu et al, 2017 ). Along similar lines, the inhibitory effects of panduratin A were documented on periodontitis-induced inflammation and osteoclastogenesis via in vitro inhibition of MAPK (intracellular enzymes involved in the response to stimuli such as inflammatory cytokines) pathways (Zhang and Li, 2015 ; Kim et al, 2018 ).…”

Section: Medical Aspects Of Periodontal Inflammationsupporting

confidence: 75%

“…Conversely, it has been shown that anti-inflammatory therapy such as inhibition of angiotensin II receptor I, is able to prevent both inflammation and bone loss, in periodontitis (Li et al, 2019a ). Other anti-inflammatory and immune regulatory processes are known to have effects on bone loss (Aral et al, 2018 ; Sima et al, 2019 ; Paula-Silva et al, 2020 ). EGFR (epidermal growth factor receptor) signaling has been found to downregulate the αvβ6 integrin, thus promoting periodontal inflammation and bone loss (Bi et al, 2020 ).…”

Section: Medical Aspects Of Periodontal Inflammationmentioning

confidence: 99%

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Periodontal Inflammation and Systemic Diseases: An Overview

2021

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Periodontitis is a common inflammatory disease of infectious origins that often evolves into a chronic condition. Aside from its importance as a stomatologic ailment, chronic periodontitis has gained relevance since it has been shown that it can develop into a systemic condition characterized by unresolved hyper-inflammation, disruption of the innate and adaptive immune system, dysbiosis of the oral, gut and other location's microbiota and other system-wide alterations that may cause, coexist or aggravate other health issues associated to elevated morbi-mortality. The relationships between the infectious, immune, inflammatory, and systemic features of periodontitis and its many related diseases are far from being fully understood and are indeed still debated. However, to date, a large body of evidence on the different biological, clinical, and policy-enabling sources of information, is available. The aim of the present work is to summarize many of these sources of information and contextualize them under a systemic inflammation framework that may set the basis to an integral vision, useful for basic, clinical, and therapeutic goals.

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Section: Medical Aspects Of Periodontal Inflammationsupporting

confidence: 75%

Section: Medical Aspects Of Periodontal Inflammationmentioning

confidence: 99%

Periodontal Inflammation and Systemic Diseases: An Overview

2021

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“…Several studies reported that osteoclastogenesis was promoted by leukotriene B4 via G protein-coupled receptors BLT1 and BLT2, and by cysteinyl leukotrienes via G protein-coupled CysLT receptors ( 42 – 45 ). 5-LO is a key enzyme of the arachidonic acid cascade that catalyzes the formation of bioactive leukotrienes, and plays an important role in inflammatory disorders and bone metabolism ( 46 ). Lee et al.…”

Section: Discussionmentioning

confidence: 99%

Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling

et al. 2022

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Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated that SOG markedly attenuated RANKL-induced osteoclast formation, F-actin ring formation, and mineral resorption by reducing the induction of key transcription factors NFATc1, c-Fos, and their target genes such as TRAP, CTSK, and DC-STAMP during osteoclastogenesis. Western blotting showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at the middle–late stage of osteoclastogenesis without altering calcineurin catalytic subunit protein phosphatase-2β-Aα expression. Moreover, GSK3β inhibitor SB415286 partially reversed SOG-induced inhibition of osteoclastogenesis, suggesting that SOG inhibits RANKL-induced osteoclastogenesis by activating GSK3β, at least in part. 5-LO gene silencing by small interfering RNA in mouse bone marrow macrophages markedly reduced RANKL-induced osteoclastogenesis by inhibiting NFATc1. However, it did not affect the phosphorylation of AKT or GSK3β, indicating that SOG exerts its inhibitory effects on osteoclastogenesis by suppressing both the independent 5-LO pathway and AKT-mediated GSK3β inactivation. In support of this, SOG significantly improved bone destruction in a lipopolysaccharide-induced mouse model of bone loss. Taken together, these results suggest a potential therapeutic effect for SOG on osteoclast-related bone lysis disease.

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“…RANKL is preferentially expressed in pre-osteoblastic cells, while its specific RANK receptor is expressed in progenitor osteoclasts. The connection between both allows a dimerization of the RANK causing the differentiation and activation of osteoclasts, which leads to the formation of a positive multinucleated TRAP cell (39). On the other hand, OPG is produced by blast cells and is considered a receptor for RANKL (40).…”

Section: Discussionmentioning

confidence: 99%