Nansi López-Valverde
Norberto Quispe-López- Department of Surgery, University of Salamanca; Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain
We present this critical review with the aim of highlighting the current status of periodontal diseases, focusing on the relevance of host modulating agents and immune pathways, in addition to new complementary therapeutic approaches for the treatment of these pathologies. Periodontal diseases are prevalent pathologies worldwide and the main cause of edentulism in the adult population. Their pathogenesis seems to be based on a dysbiosis of the oral microbiota that interacts with the host’s immune defenses and is responsible for the inflammatory/immune response, which would be modified by a number of conditions such as individual susceptibility, environmental and sociodemographic factors, certain systemic pathologies and the individual’s genetic condition, among others. Numerous studies have reported on the complex web of inflammatory mediators in periodontal disease and their role in tissue destruction as well as in homeostatic imbalance. Precisely, the role of epigenetics as a modifier of the host genetic condition has captured research attention in recent years. Therefore, this mini-review first discusses an updated etiological hypothesis of periodontal disease and the roles of certain cytokines in the immune response. In addition, the latest therapeutic trends with new developments and future perspectives are summarized.
1 Introduction
Periodontal diseases are considered a group of pathologies of inflammatory origin. Unlike periodontitis in which the lesions produced by the alteration of the dental supporting tissues are irreversible, gingivitis is reversible after resolutive treatment of gingival inflammation (Chapple et al., 2018).
Polymicrobial aggression, together with the host response and bacterial imbalance or dysbiosis, would be ultimately responsible for the establishment of the pathology (Hajishengallis et al., 2020 2000; Kinane et al., 2017); however, although more than 800 pathogens have been identified in different human biofilms (bacteria, archaea, protozoa, fungi and viruses) (Mosaddad et al., 2019; Antezack et al., 2023), it is still unknown which species cause the disease. This dysbiotic state, together with an exaggerated immune reaction, are major drivers of the inflammation and tissue damage detected in periodontal disease (Lamont and Hajishengallis, 2015). Additionally, individual susceptibility can be dictated by modifiers of the inflammatory response like environmental and sociodemographic factors, certain systemic pathologies, and the genetic condition of the host, among others, should be added (Scapoli et al., 2005; Shapira et al., 2005; Alawaji et al., 2022). This last situation is an interesting and intense focus of research trying to identify polymorphisms associated with different periodontal pathologies, and currently, it is considered that certain genes could be involved in periodontitis and that their genotypes could vary in different individuals or ethnic groups (Loos and Van Dyke, 2020 2000; Imamura et al., 2008). Another important aspect to consider would be epigenetic variants as modifiers of gene expression, acquired throughout life or inherited (Schulz et al., 2016; Jurdziński et al., 2020), although possible epigenetic implications in inflammatory pathologies have not been shown to be clinically relevant, and the role of epigenomic drugs is considered “potentially” novel in improving periodontal disease status (Barros et al., 2018 2000).
Bacterial dysbiosis induces exaggerated levels of inflammatory mediators, such as IL-1, prostaglandin E2 and tumor necrosis factor α (TNF-α) in subjects suffering from the disease, and initiates a cycle of exaggerated inflammatory response, aggravating tissue destruction (Gasmi Benahmed et al., 2022). Certain studies have shown that colonization by Porphyromona gingivalis, even at low levels, can alter the oral microbial homeostatic balance and trigger periodontal disease through inflammation and bone loss, produced by the dysbiotic state (Maekawa et al., 2014; Gasmi Benahmed et al., 2023). On the other hand, this homeostatic imbalance may undergo variations throughout the individual’s existence and be affected by conditions such as aging, epigenetic conditions and certain comorbidities that modify immune function (Abdulkareem et al., 2023).
The existence of dental biofilms (dental plaque) on the tooth surface is considered a natural phenomenon that helps to maintain the oral microbiota, preventing the invasion of exogenous species (Epsley et al., 2021), but dental plaque around the dental neck generates gingival inflammation and increased crevicular fluid, which is an excellent medium for the development of immunoglobulins, collagen degradation products, cytokines, serum proteins, etc. and above all of immune cells and desquamation of the internal epithelium of the periodontal pocket, together with the remains of gingival collagen degradation. In addition, the anoxic state of the environment, contribute to an increase in prevalence of anaerobic pathogens (Peng et al., 2024).
This mini-review aims to give a high-level overview on the current knowledge of the pathogenesis of periodontal disease, and the current evolution of its treatment, through new advances and emerging concepts, exposing different controversies and future perspectives. For more in-depth analyses of the literature, we direct readers to recent rigorous reviews (Marsh, 2010; Ray and Yung, 2018; Suárez et al., 2020).
2 Recently discovered inflammatory pathways in periodontitis
2.1 Resolvins
Granulocyte neutrophils or polymorphonuclear neutrophils (PMNs) are abundant in inflamed tissues and resolution of inflammation involves their elimination (Ariel et al., 2006); therefore, many therapeutic approaches are based on blocking the activation of inflammation, such as nonsteroidal anti-inflammatory drugs and tumor necrosis factor (TNF) inhibitors. Cyclooxygenase inhibitor drugs are a clear example of anti-inflammatory drugs that block prostaglandin synthesis (Kantarci et al., 2006 2000; Kirkwood et al., 2007 2000; Schonfeld, 2010). The lipoxins released by acetylsalicylic acid (ASA) and its synthetic derivatives, despite their toxic effect, favor the resolution of inflammation, especially by reducing the influx of neutrophils (Serhan, 2005). Precisely, a certain ω-3 fatty acid (eicosapentaenoic acid) is metabolized by cyclooxygenase-2 modified by ASA, giving rise to a small molecule (RvE1) capable of favoring the resolution of inflammation (Schwab and Serhan, 2006).
Resolvins are bioactive products of ω-3 fatty acids that counteract proinflammatory signals by retaining leukocyte recruitment. Hasturk et al. in an in vivo study suggested that RvE1, in topical application in rabbits with periodontitis, protected against inflammation-induced bone and soft tissue loss (Hasturk et al., 2006). Similarly, Lee et al (Lee et al., 2016). demonstrated in a rat model with ligation periodontitis that topical treatment with RvE1 prevented bone loss by reducing osteoclast density and inflammation-related gene expression, along with modifications in subgingival microbiota and bacterial growth conditions. This is despite the important role of inflammation in this regard. Hasturk et al. reported in an in vivo study, regeneration of hard and soft tissues, destroyed by inflammatory diseases by monotherapy of activation of inflammation resolution pathways with RvE1, obtained from ω-3, demonstrating the role of local inflammation in tissue destruction (Hasturk et al., 2007).
2.2 Inflammasomes, pyroptosis and their role in periodontal pathology
Inflammasomes are protein complexes located in the cell cytoplasm that act as sensors and mediate the development of inflammation (Paerewijck and Lamkanfi, 2022). More and more studies are investigating biomarkers of periodontitis (Isaza-Guzmán et al., 2017; Isola et al., 2022) and there is increasing evidence that inflammasomes are involved in the periodontal immune response, controlling invading microorganisms (Li et al., 2021b; Sordi et al., 2021). It is known that excessive activation of inflammasomes leads to inflammatory dyscontrol (by the release of proinflammatory cytokines IL-1β, IL-18), cytokine storm and tissue damage, and that patients with periodontal pathologies present elevated levels of certain inflammasomes in saliva, proportional to the severity of the disease. On the other hand, the oral microbiota deregulates the tissue expression of the NLRP3 inflammasome, which aggravates periodontal inflammation (Zhao et al., 2022; Didilescu et al., 2024). Polymerase chain reaction (PCR), used for the detection of periodontal pathogens in aggressive periodontitis, showed an increase of IL-1β, produced by macrophages and monocytes, in early stages of inflammation, which would signify the important role of local inflammation on systemic inflammation (Noack et al., 2001; Ebersole et al., 2002; Salzberg et al., 2006; Lopez-Castejon and Brough, 2011).
Periodontal pathogens, such as P. gingivalis and Fusobacterium nucleatum, are known to activate the canonical NLRP3 inflammasome (Aral et al., 2020). Activated canonical NLRP3 directly stimulates caspase-1 (a protein mediating the processes of programmed cell death, or apoptosis), leading to maturation and secretion of proinflammatory cytokines (Man et al., 2017).
The cytokine IL-1β is instrumental in the development of periodontal pathology and it is well known that NLRP3 is involved in its maturation (Chen Y. et al., 2021; Li et al., 2021b). Thus, the abnormal activation or overexpression of NLRP3 in osteoclasts, osteoblasts, fibroblasts, and immune cells is considered to play a critical role in the pathogenesis of periodontal disease (Zhao et al., 2022).
Osteoclasts play an important role in bone loss processes and excessive osteoclastic activity leads to bone destructive pathologies. IL-1β has been observed to potentiate osteoclastogenesis through extracellular matrix degradation (Zhou et al., 2022; Otsuka et al., 2023) (Figure 1).
Figure 1. Diagram of causative-predisposing agents and the role of inflammasomes in pyroptosis, osteoclastogenesis and bone loss in periodontal disease.
Using a mouse model of induced periodontitis, Chen et al (Chen Y. et al., 2021), were able to suppress alveolar bone loss using a specific NLRP3 inhibitor, which also reduced IL-1β activation and osteoclast differentiation. The NLRP3 inflammasome has also been observed to play an important role in osteoclastogenesis during aging (Zang et al., 2020). A recent review conducted by Bakhshi et al (Bakhshi and Shamsi, 2022). reported that the NLRP3 inflammasome may be involved in the pathogenesis of several inflammatory and autoimmune diseases such as type 2 diabetes mellitus, and that inhibition of this inflammasome could be a useful treatment option for inflammatory diseases, by reducing the production of the cytokine IL-1β. Together, this supports targeting the inflammasome to treat multiple inflammatory diseases.
Osteoblasts participate in bone mineralization (Zhao et al., 2014) but, when infected by certain gram-negative pathogens, such as Aggregatibacter actinomycetemcomitans, they generate IL-1β and programmed cell death, mediated by NLRP3 activation (Herbert et al., 2016; Wang et al., 2017). Reactive oxygen species (ROS) are a determining factor in NLRP3 activation and certain research has demonstrated the role of oxidative stress (OS) in the pathogenesis of periodontal disease and periodontal tissue damage, as well as the beneficial role of antioxidant therapies (Sczepanik et al., 2020 2000; Liu et al., 2020; López-Valverde et al., 2024). Bone regeneration is a complex process in which, in addition to metabolism, differentiation and cell migration, the immune system is involved (Ye et al., 2021). This system is associated with bone loss and it has been shown that inflammatory stimuli, due to an immune imbalance, can cause an alteration of bone turnover through osteoclastic differentiation, together with a slowing of osteoblastic differentiation, which could generate different bone metabolic pathologies (Xiong et al., 2022). The bone formation/resorption balance goes through the regulation of pyroptosis and it is known that NLRP3 is able to produce IL-1β and trigger pyroptosis in response to molecular patterns associated with periodontal pathogens; however, an inappropriate activation of the inflammasome, may generate an environment prone to inflammation and massive cell destruction, as occurs in the bone destruction characteristic of periodontitis (Chen Q. et al., 2021). Thus, pyroptosis and certain cytokines, such as IL-1β, are maintainers of homeostasis and drivers of the individual’s innate immune response, shaping his or her adaptive immunity (Li and Jiang, 2023).
On the other hand, the important role of periodontal ligament fibroblasts in the regenerative functions of alveolar bone and in inflammation through the production of proinflammatory cytokines that damage the periodontal ligament is noteworthy (Isaka et al., 2001). Gram-negative bacterial lipopolysaccharide (LPS) is a major component of the outer membrane and plays a key role in host-pathogen interactions with the innate immune system. In vitro studies in human periodontal ligament cells have shown that LPS would be able to trigger pyroptotic cell death in periodontal ligament cells and promote the generation and secretion of proinflammatory cytokines (Zhang et al., 2021). Zhang et al. in a recent study in a rat model reported a potent virulence factor secreted by certain periodontal pathogens, such as F. nucleatum and P. gingivalis, that would be involved in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues and would be able to trigger the activation of NLRP3, the neutralization of which would be instrumental in the treatment of periodontitis (Zhang et al., 2024).
However, there are few studies linking NLRP3 to periodontal ligament fibroblasts, which would warrant further study. PMNs are the most abundant leukocyte species in inflamed periodontal tissues (Ginesin et al., 2023). Dysfunction of PMNs is determinant in periodontitis and related comorbidities. Inflammatory persistence of periodontitis can lead to aberrant neutrophil activation and sustained release of proinflammatory mediators, resulting in tissue damage, bone resorption, and progression of periodontal disease (Bassani et al., 2023). The infiltration of PMNs at the periodontal lesion site is dependent on the expression of NLRP3 (Han et al., 2022). Surlin et al. in a study of 62 participants to evaluate the impact that periodontal disease and chronic hepatitis C might have on NLRP3 levels, along with increased local inflammatory reaction with periodontal clinical consequences, found significantly elevated levels for NLRP3 in the hepatitis C and periodontitis group compared to the non-periodontitis groups. Furthermore, they found a positive correlation of NLRP3 levels, together with certain metabolic parameters, including glucose, aspartatetransferase and alaninetransferase levels, demonstrating that chronic hepatitis C and periodontal disease could significantly influence the up-regulation of NLRP3 and its components, possibly contributing to an increased local inflammatory reaction (Surlin et al., 2021).
Cellular self-destruction contributes to homeostasis and to the defense of the human organism against pathogen aggression. One of the mechanisms of self-destruction, apoptosis, is described as a programmed and active process that prevents inflammation, unlike necrosis, and is characterized as a passive and accidental cell death (Fink and Cookson, 2005). Another mechanism of programmed cell death, pyroptosis, is characterized by cell swelling and subsequent rupture of the cytoplasmic membrane, releasing a large number of molecules that trigger a strong inflammatory response, with subsequent recruitment of immune system cells (Yu et al., 2021). In inflammatory pathologies, such as periodontal diseases, the responsible pathogens can trigger pyroptosis of host cells through NLRP3 activation. This would result in the subsequent release of proinflammatory cytokines, increasing the host immune response and thus tissue destruction (Chen et al., 2024).
Several studies have highlighted the role of pyroptosis in periodontal disease, demonstrating that LPS from P. gingivalis would be able to induce gingivitis, destroy the epithelial connection and increase the expression of pyroptosis-associated proteins (Li et al., 2021a; Li YY. et al., 2021; Lv et al., 2021; Yang et al., 2021). Pan et al. found bidirectionality in the up-regulation of IL-1β in PMNs as a mechanism of cell death in periodontitis, underlining the importance of this finding in the pathogenesis of the disease (Pan et al., 2023).
3 Periodontal therapeutics
Although periodontal diseases are highly prevalent and functionally and esthetically disabling, there is a lack of unified criteria for their diagnosis. Understanding the pathognomonic mechanisms that cause them is key to developing preventive measures and effective treatments, as traditional surgical treatments are often ineffective, especially in patients with exaggerated immune responses.
3.1 Inflammasome inhibitor drugs
NLRP3 is known to be involved in a wide variety of infections directly related to inflammatory and degenerative pathologies (Stout-Delgado et al., 2016; Shen et al., 2020; Liu et al., 2022; Ye et al., 2023), but drugs directed against NLRP3 are scarce. Recently, Ye et al (Ye et al., 2023). have proposed peptides as more suitable remedies against small molecules, with the advantage of being more potent, less toxic and having fewer unwanted effects. Coll et al (Coll et al., 2015). proposed a specific small molecule inhibitor of NLRP3, at reduced doses, which has a potent action in numerous pathologies of inflammatory origin. Subsequently, other studies have shown that MCC950 would enhance neuroinflammation-related neurogenesis by disrupting NLRP3 activation (Gordon et al., 2018). All this would lead one to believe that MCC950 could suppress NLRP3 (Tang et al., 2017); however, despite undergoing phase II clinical trials, the research was abandoned due to liver damage in some cases (Mangan et al., 2018). Although not evaluated in periodontal disease models, Jiang et al (Jiang et al., 2017), in autoinflammatory syndrome mouse models, identified a small molecule, CY-09, capable of specifically inhibiting NLRP3 and suppressing IL-1β production.
3.2 Systemic antibiotics
Systemic antibiotics such as metronidazole, amoxicillin or ciprofloxacin are still used in the treatment of periodontitis and are capable of eliminating or greatly reducing the main periodontal pathogens (Slots, 2020 2000), but the adverse reactions and side effects of this type of treatment make it necessary to develop new therapies that do not have these drawbacks.
3.3 Semi-synthetic derivatives of Artemisinin
Artesunate, a natural peroxide, derived from the herb Artemisia Annua, has been proposed for its demonstrated anti-inflammatory and immunomodulatory effects in different bone pathologies (Zhang, 2020). Huang et al (Huang et al., 2022). demonstrated its efficacy in an osteoporotic murine model, in which it produced a marked increase in alkaline phosphatase activity and osteogenesis-related molecules. Recently, a study by Wang et al (Wang et al., 2023). in rats with ligation-induced periodontitis, showed that artesunate was able to reduce alveolar bone loss generated by periodontitis and suppress osteoclastogenesis, as well as stimulate osteogenic potential and reduce cytokine expression under inflammatory conditions. Other investigations have also highlighted the therapeutic potential of artesunate on inflammatory destruction, due to its endoperoxide group (Su et al., 2021; Wang et al., 2022).
3.4 Sulfonylureas
Glyburide is a hypoglycemic sulfonylurea used for the treatment of type 2 diabetes mellitus that has also demonstrated anti-inflammatory capacity, both in humans and in animal models. While its ability to suppress IL-1β activation and release is unclear, it seems likely that this ability would only be present in the absence of pyroptosis (Roglic and Norris, 2018; Zahid et al., 2019). In addition, its ability to inhibit inflammatory cell infiltration, osteoclast formation and bone resorption has been demonstrated in rats with experimental periodontitis, suggesting that glyburide may be therapeutically useful as a treatment for periodontal diseases (Kawahara et al., 2020).
These therapeutic targets against inflammasomes are promising candidates, but further research must be conducted to ensure efficacy against periodontal disease and safety in humans.
4 Control of immune response; new therapies
The role of cell destruction and cell death in periodontitis remains largely unknown and therefore, necessary to further explore this aspect to clarify its implications.
It has been reported that both periodontitis and rheumatoid arthritis may share the presence of periodontal pathogens that promote protein shedding, resulting in anti-citrullinated protein antibodies, a typical trigger for autoimmune pathologies (Corrêa et al., 2019). A meta-analysis by Zamri and de Vries (2020) investigated the duration of anti-TNF-α treatment on periodontal clinical parameters, finding that treatments of less than 6 months were beneficial, whereas those of more than 6 months were associated with higher gingival indices and bleeding on probing, possibly due to the development of anti-drug antibodies. Similarly, another recent review (Inchingolo et al., 2023) that investigated the effect of antirheumatic drugs on periodontal indices and cytokine levels in periodontitis demonstrated beneficial effects of these drugs on clinical and immunological parameters of the periodontium. It is known that B lymphocytes are present in areas of chronic periodontal inflammation, stimulating osteoclasts through the genesis of IL-6, IL-17 and Receptor Activating Nuclear Factor κ B Ligand (RANKL) and that patients treated with B-lymphocyte blocking drugs presented less aggressive forms of periodontitis (Coat et al., 2015); however, the use of this type of drugs is associated with a number of side effects, such as skin reactions, cardiac failure and hepatotoxicity, which limits their usefulness in the treatment of periodontal pathologies (Zamri and de Vries, 2020).
Probiotics and ω-3 fatty acid supplements are being promoted as potential therapeutic candidates in the treatment of inflammatory pathologies. An extensive review by Homayouni et al (Homayouni Rad et al., 2023). highlighted the important role of probiotics as antioxidant producers and plaque formation preventive agents. Allaker and Stephen (2017) advocated them as modulators of host dysbiosis and immune-inflammatory pathways, thus reducing the destructive capacity of periodontal disease. However, attention has been drawn to the potential risks of prolonged consumption in subjects with a weakened immune system (Tegegne and Kebede, 2022).
The reduction of periodontal inflammation with ω-3 fatty acids, as a modulatory therapy and observing its effects on pocket probing depth and clinical attachment level, has been carried out in different studies as an adjunct to surgical therapy, demonstrating its efficacy, despite scarce clinical evidence (Van Ravensteijn et al., 2022).
Statins are cholesterol-lowering drugs with anti-inflammatory, anticoagulant and antioxidant effects (Biasucci et al., 2010), in addition to other benefits on endothelial cell function and modulation of the inflammatory response. In the treatment of periodontitis, they have been used in preclinical studies, locally in periodontal pockets, observing an increase in antioxidants, together with an increase in anti-inflammatory mediators and a reduction in bone resorption (Sousa et al., 2016).
The use of bisphosphonates in the treatment of periodontitis, despite their inhibitory effect on bone destruction, is controversial, mainly due to the side effect of mandibular osteonecrosis (Aguirre et al., 2021) (Figure 2).
Figure 2. Representative diagram of future therapeutic targets in periodontal disease.
5 Conclusions and perspectives
Although dysbiosis is the primary driver of periodontal disease, the NLRP3 inflammasome, which mediates the maturation of the cytokine IL-1β, plays a crucial role in its pathogenesis. The limited efficacy of traditional surgical treatments in some cases highlights the potential of alternative therapies, including systemic antibiotics, NLRP3 inhibitors and anti-inflammatory drugs. However, their use is often hampered by adverse reactions and other drawbacks. Although treatments such as ω-3 fatty acid supplements, probiotics, statins and bisphosphonates offer some immune modulation, their long-term use carries potential risks. These challenges underscore the need for further research and development of new therapeutic options.
Author contributions
NL-V: Writing – original draft, Writing – review & editing, Conceptualization, Investigation. NQ-L: Writing – original draft, Writing – review & editing. JB: Writing – original draft, Writing – review & editing.
Funding
The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
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References
Abdulkareem, A. A., Al-Taweel, F. B., Al-Sharqi, A. J. B., Gul, S. S., Sha, A., Chapple, I. L. C. (2023). Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis. J. Oral. Microbiol. 15, 2197779. doi: 10.1080/20002297.2023.2197779
Aguirre, J. I., Castillo, E. J., Kimmel, D. B. (2021). Preclinical models of medication-related osteonecrosis of the jaw (MRONJ). Bone. 153, 116184. doi: 10.1016/j.bone.2021.116184
Alawaji, Y. N., Alshammari, A., Mostafa, N., Carvalho, R. M., Aleksejuniene, J. (2022). Periodontal disease prevalence, extent, and risk associations in untreated individuals. Clin. Exp. Dent. Res. 8, 380–394. doi: 10.1002/cre2.526
Allaker, R. P., Stephen, A. S. (2017). Use of probiotics and oral health. Curr. Oral. Health Rep. 4, 309–318. doi: 10.1007/s40496-017-0159-6
Antezack, A., Etchecopar-Etchart, D., La Scola, B., Monnet-Corti, V. (2023). New putative periodontopathogens and periodontal health-associated species: A systematic review and meta-analysis. J. Periodontal Res. 58, 893–906. doi: 10.1111/jre.13173
Aral, K., Milward, M. R., Kapila, Y., Berdeli, A., Cooper, P. R. (2020). Inflammasomes and their regulation in periodontal disease: A review. J. Periodontal Res. 55, 473–487. doi: 10.1111/jre.12733
Ariel, A., Fredman, G., Sun, Y. P., Kantarci, A., Van Dyke, T. E., Luster, A. D., et al. (2006). Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat. Immunol. 7, 1209–1216. doi: 10.1038/ni1392
Bakhshi, S., Shamsi, S. (2022). MCC950 in the treatment of NLRP3-mediated inflammatory diseases: Latest evidence and therapeutic outcomes. Int. Immunopharmacol. 106, 108595. doi: 10.1016/j.intimp.2022.108595
Barros, S. P., Hefni, E., Nepomuceno, R., Offenbacher, S., North, K. (2018). Targeting epigenetic mechanisms in periodontal diseases. Periodontol 2000 78, 174–184. doi: 10.1111/prd.12231
Bassani, B., Cucchiara, M., Butera, A., Kayali, O., Chiesa, A., Palano, M. T., et al. (2023). Neutrophils' Contribution to periodontitis and periodontitis-associated cardiovascular diseases. Int. J. Mol. Sci. 24, 15370. doi: 10.3390/ijms242015370
Biasucci, L. M., Biasillo, G., Stefanelli, A. (2010). Inflammatory markers, cholesterol and statins: pathophysiological role and clinical importance. Clin. Chem. Lab. Med. 48, 1685–1691. doi: 10.1515/CCLM.2010.277
Chapple, I. L. C., Mealey, B. L., Van Dyke, T. E., Bartold, P. M., Dommisch, H., Eickholz, P., et al. (2018). Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Periodontol. 89, Suppl 1, S74–S84. doi: 10.1002/JPER.17-0719
Chen, L., Tang, Z., Fu, L., Xie, Y., Xu, J., Xia, H., et al. (2024). The critical role of pyroptosis in peri-implantitis. J. Inflammation Res. 17, 1621–1642. doi: 10.2147/JIR.S450706
Chen, Q., Liu, X., Wang, D., Zheng, J., Chen, L., Xie, Q., et al. (2021). Periodontal inflammation-triggered by periodontal ligament stem cell pyroptosis exacerbates periodontitis. Front. Cell Dev. Biol. 9. doi: 10.3389/fcell.2021.663037
Chen, Y., Yang, Q., Lv, C., Chen, Y., Zhao, W., Li, W., et al. (2021). NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation. Cell Prolif. 54, e12973. doi: 10.1111/cpr.12973
Coat, J., Demoersman, J., Beuzit, S., Cornec, D., Devauchelle-Pensec, V., Saraux, A., et al. (2015). Anti-B lymphocyte immunotherapy is associated with improvement of periodontal status in subjects with rheumatoid arthritis. J. Clin. Periodontol. 42, 817–823. doi: 10.1111/jcpe.12433
Coll, R. C., Robertson, A. A., Chae, J. J., Higgins, S. C., Muñoz-Planillo, R., Inserra, M. C., et al. (2015). A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 21, 248–255. doi: 10.1038/nm.3806
Corrêa, J. D., Fernandes, G. R., Calderaro, D. C., Mendonça, S. M. S., Silva, J. M., Albiero, M. L., et al. (2019). Oral microbial dysbiosis linked to worsened periodontal condition in rheumatoid arthritis patients. Sci. Rep. 9, 8379. doi: 10.1038/s41598-019-44674-6
Didilescu, A. C., Chinthamani, S., Scannapieco, F. A., Sharma, A. (2024). NLRP3 inflammasome activity and periodontal disease pathogenesis-A bidirectional relationship. Oral. Dis. 30, 4069–4077. doi: 10.1111/odi.15005
Ebersole, J. L., Cappelli, D., Mathys, E. C., Steffen, M. J., Singer., R. E., Montgomery, M., et al. (2002). Periodontitis in humans and non-human primates: oral-systemic linkage inducing acute phase proteins. Ann. Periodontol. 7, 102–111. doi: 10.1902/annals.2002.7.1.102
Epsley, S., Tadros, S., Farid, A., Kargilis, D., Mehta, S., Rajapakse, C. S. (2021). The effect of inflammation on bone. Front. Physiol. 11. doi: 10.3389/fphys.2020.511799
Fink, S. L., Cookson, B. T. (2005). Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 73, 1907–1916. doi: 10.1128/IAI.73.4.1907-1916.2005
Gasmi Benahmed, A., Kumar Mujawdiya, P., Noor, S., Gasmi., A. (2022). Porphyromonas gingivalis in the development of periodontitis: impact on dysbiosis and inflammation. Arch. Razi Inst. 77, 1539–1551. doi: 10.22092/ARI.2021.356596.1875
Gasmi Benahmed, A., Noor, S., Menzel, A., Gasmi, A. (2023). A boolean network approach to study the mechanism associated with inflammatory response induced by porphyromonas gingivalis. Arch. Razi Inst. 78, 1–7. doi: 10.22092/ARI.2021.356604.1877
Ginesin, O., Mayer, Y., Gabay, E., Rotenberg, D., Machtei, E. E., Coyac, B. R., et al. (2023). Revealing leukocyte populations in human peri-implantitis and periodontitis using flow cytometry. Clin. Oral. Investig. 27, 5499–5508. doi: 10.1007/s00784-023-05168-y
Gordon, R., Albornoz, E. A., Christie, D. C., Langley, M. R., Kumar, V., Mantovani, S., et al. (2018). Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Sci. Transl. Med. 10, eaah4066. doi: 10.1126/scitranslmed.aah4066
Hajishengallis, G., Chavakis, T., Lambris, J. D. (2020). Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy. Periodontol 2000 84, 14–34. doi: 10.1111/prd.12331
Han, Y., Huang, Y., Gao, P., Yang, Q., Jia, L., Zheng, Y., et al. (2022). Leptin aggravates periodontitis by promoting M1 polarization via NLRP3. J. Dent. Res. 101, 675–685. doi: 10.1177/00220345211059418
Hasturk, H., Kantarci, A., Goguet-Surmenian, E., Blackwood, A., Andry, C., Serhan, C. N., et al. (2007). Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J. Immunol. 179, 7021–7029. doi: 10.4049/jimmunol.179.10.7021
Hasturk, H., Kantarci, A., Ohira, T., Arita, M., Ebrahimi, N., Chiang, N., et al. (2006). RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J. 20, 401–403. doi: 10.1096/fj.05-4724fje
Herbert, B. A., Novince, C. M., Kirkwood, K. L. (2016). Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis. Mol. Oral. Microbiol. 31, 207–227. doi: 10.1111/omi.12119
Homayouni Rad, A., Pourjafar, H., Mirzakhani, E. (2023). A comprehensive review of the application of probiotics and postbiotics in oral health. Front. Cell Infect. Microbiol. 13. doi: 10.3389/fcimb.2023.1120995
Huang, M. Z., Chen, H. Y., Peng, G. X., Sun, H., Peng, H. C., Li, H. Y., et al. (2022). Exosomes from artesunate-treated bone marrow-derived mesenchymal stem cells transferring SNHG7 to promote osteogenesis via TAF15-RUNX2 pathway. Regener. Med. 17, 819–833. doi: 10.2217/rme-2022-0065
Imamura, Y., Fujigaki, Y., Oomori, Y., Kuno, T., Ota, N., Wang, P. L. (2008). Polymorphism of genes encoding toll-like receptors and inflammatory cytokines in periodontal disease in the Japanese population. J. Int. Acad. Periodontol. 10, 95–102.
Inchingolo, F., Inchingolo, A. M., Avantario, P., Settanni, V., Fatone, M. C., Piras, F., et al. (2023). The effects of periodontal treatment on rheumatoid arthritis and of anti-rheumatic drugs on periodontitis: A systematic review. Int. J. Mol. Sci. 24, 17228. doi: 10.3390/ijms242417228
Isaka, J., Ohazama, A., Kobayashi, M., Nagashima, C., Takiguchi, T., Kawasaki, H., et al. (2001). Participation of periodontal ligament cells with regeneration of alveolar bone. J. Periodontol. 72, 314–323. doi: 10.1902/jop.2001.72.3.314
Isaza-Guzmán, D. M., Medina-Piedrahíta, V. M., Gutiérrez-Henao, C., Tobón-Arroyave, S. I. (2017). Salivary levels of NLRP3 inflammasome-related proteins as potential biomarkers of periodontal clinical status. J. Periodontol. 88, 1329–1338. doi: 10.1902/jop.2017.170244
Isola, G., Polizzi, A., Santonocito, S., Alibrandi, A., Williams, R. C. (2022). Periodontitis activates the NLRP3 inflammasome in serum and saliva. J. Periodontol. 93, 135–145. doi: 10.1002/JPER.21-0049
Jiang, H., He, H., Chen, Y., Huang, W., Cheng, J., Ye, J., et al. (2017). Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J. Exp. Med. 214, 3219–3238. doi: 10.1084/jem.20171419
Jurdziński, K. T., Potempa, J., Grabiec, A. M. (2020). Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential. Clin. Epigenetics. 12, 186. doi: 10.1186/s13148-020-00982-7
Kantarci, A., Hasturk, H., Van Dyke, T. E. (2006). Host-mediated resolution of inflammation in periodontal diseases. Periodontol 2000 40, 144–163. doi: 10.1111/j.1600-0757.2005.00145.x
Kawahara, Y., Kaneko, T., Yoshinaga, Y., Arita, Y., Nakamura, K., Koga, C., et al. (2020). Effects of sulfonylureas on periodontopathic bacteria-induced inflammation. J. Dent. Res. 99, 830–838. doi: 10.1177/0022034520913250
Kinane, D. F., Stathopoulou, P. G., Papapanou, P. N. (2017). Periodontal diseases. Nat. Rev. Dis. Primers. 3, 17038. doi: 10.1038/nrdp.2017.38
Kirkwood, K. L., Cirelli, J. A., Rogers, J. E., Giannobile, W. V. (2007). Novel host response therapeutic approaches to treat periodontal diseases. Periodontol 2000 43, 294–315. doi: 10.1111/j.1600-0757.2006.00166.x
Lamont, R. J., Hajishengallis, G. (2015). Polymicrobial synergy and dysbiosis in inflammatory disease. Trends Mol. Med. 21, 172–183. doi: 10.1016/j.molmed.2014.11.004
Lee, C. T., Teles, R., Kantarci, A., Chen, T., McCafferty, J., Starr, J. R., et al. (2016). Resolvin E1 reverses experimental periodontitis and dysbiosis. J. Immunol. 197, 2796–2806. doi: 10.4049/jimmunol.1600859
Li, Y. Y., Cai, Q., Li, B. S., Qiao, S. W., Jiang, J. Y., Wang, D., et al. (2021). The effect of porphyromonas gingivalis lipopolysaccharide on the pyroptosis of gingival fibroblasts. Inflammation. 44, 846–858. doi: 10.1007/s10753-020-01379-7
Li, Y., Jiang, Q. (2023). Uncoupled pyroptosis and IL-1β secretion downstream of inflammasome signaling. Front. Immunol. 14. doi: 10.3389/fimmu.2023.1128358
Li, Y., Li, B., Liu, Y., Wang, H., He, M., Liu, Y., et al. (2021a). Porphyromonas gingivalis lipopolysaccharide affects oral epithelial connections via pyroptosis. J. Dent. Sci. 16, 1255–1263. doi: 10.1016/j.jds.2021.01.003
Li, Y., Ling, J., Jiang, Q. (2021b). Inflammasomes in alveolar bone loss. Front. Immunol. 12. doi: 10.3389/fimmu.2021.691013
Liu, S., Du, J., Li, D., Yang, P., Kou, Y., Li, C., et al. (2020). Oxidative stress induced pyroptosis leads to osteogenic dysfunction of MG63 cells. J. Mol. Histol. 51, 221–232. doi: 10.1007/s10735-020-09874-9
Liu, Y., Xu, X., Lei, W., Hou, Y., Zhang, Y., Tang, R., et al. (2022). The NLRP3 inflammasome in fibrosis and aging: The known unknowns. Ageing Res. Rev. 79, 101638. doi: 10.1016/j.arr.2022.101638
Loos, B. G., Van Dyke, T. E. (2020). The role of inflammation and genetics in periodontal disease. Periodontol 2000 83, 26–39. doi: 10.1111/prd.12297
Lopez-Castejon, G., Brough, D. (2011). Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 22, 189–195. doi: 10.1016/j.cytogfr.2011.10.001
López-Valverde, N., López-Valverde, A., Macedo de Sousa, B., Blanco Rueda, J. A. (2024). Systematic review and meta-analysis of the antioxidant capacity of lycopene in the treatment of periodontal disease. Front. Bioeng Biotechnol. 11. doi: 10.3389/fbioe.2023.1309851
Lv, X., Fan, C., Jiang, Z., Wang, W., Qiu, X., Ji, Q. (2021). Isoliquiritigenin alleviates P. gingivalis-LPS/ATP-induced pyroptosis by inhibiting NF-κB/ NLRP3/GSDMD signals in human gingival fibroblasts. Int. Immunopharmacol 101, 108338. doi: 10.1016/j.intimp.2021.108338
Maekawa, T., Krauss, J. L., Abe, T., Jotwani, R., Triantafilou, M., Triantafilou, K., et al. (2014). Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe 15, 768–778. doi: 10.1016/j.chom.2014.05.012
Man, S. M., Karki, R., Kanneganti, T. D. (2017). Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol. Rev. 277, 61–75. doi: 10.1111/imr.12534
Mangan, M. S. J., Olhava, E. J., Roush, W. R., Seidel, H. M., Glick, G. D., Latz, E. (2018). Targeting the NLRP3 inflammasome in inflammatory diseases. Nat. Rev. Drug Discovery 17, 588–606. doi: 10.1038/nrd.2018.97
Marsh, P. D. (2010). Microbiology of dental plaque biofilms and their role in oral health and caries. Dent. Clin. North Am. 54, 441–454. doi: 10.1016/j.cden.2010.03.002
Mosaddad, S. A., Tahmasebi, E., Yazdanian, A., Rezvani, M. B., Seifalian, A., Yazdanian, M., et al. (2019). Oral microbial biofilms: an update. Eur. J. Clin. Microbiol. Infect. Dis. 38, 2005–2019. doi: 10.1007/s10096-019-03641-9
Noack, B., Genco, R. J., Trevisan, M., Grossi, S., Zambon, J. J., De Nardin, E. (2001). Periodontal infections contribute to elevated systemic C-reactive protein level. J. Periodontol. 72, 1221–1227. doi: 10.1902/jop.2000.72.9.1221
Otsuka, Y., Kondo, T., Aoki, H., Goto, Y., Kawaguchi, Y., Waguri-Nagaya, Y., et al. (2023). IL-1β promotes osteoclastogenesis by increasing the expression of IGF2 and chemokines in non-osteoclastic cells. J. Pharmacol. Sci. 151, 1–8. doi: 10.1016/j.jphs.2022.10.007
Paerewijck, O., Lamkanfi, M. (2022). The human inflammasomes. Mol. Aspects Med. 88, 101100. doi: 10.1016/j.mam.2022.101100
Pan, S., Li, Y., He, H., Cheng, S., Li, J., Pathak, J. L. (2023). Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis. Front. Pharmacol. 13. doi: 10.3389/fphar.2022.1098851
Peng, S., Fu, H., Li, R., Li, H., Wang, S., Li, B., et al. (2024). A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy. J. Nanobiotechnology. 22, 359. doi: 10.1186/s12951-024-02592-4
Ray, D., Yung, R. (2018). Immune senescence, epigenetics and autoimmunity. Clin. Immunol. 196, 59–63. doi: 10.1016/j.clim.2018.04.002
Roglic, G., Norris, S. L. (2018). Medicines for treatment intensification in type 2 diabetes and type of insulin in type 1 and type 2 diabetes in low-resource settings: synopsis of the world health organization guidelines on second- and third-line medicines and type of insulin for the control of blood glucose levels in nonpregnant adults with diabetes mellitus. Ann. Intern. Med. 169, 394–397. doi: 10.7326/M18-1149
Salzberg, T. N., Overstreet, B. T., Rogers, J. D., Califano, J. V., Best, A. M., Schenkein, H. A. (2006). C-reactive protein levels in patients with aggressive periodontitis. J. Periodontol. 77, 933–939. doi: 10.1902/jop.2006.050165
Scapoli, C., Tatakis, D. N., Mamolini, E., Trombelli, L. (2005). Modulation of clinical expression of plaque-induced gingivitis: interleukin-1 gene cluster polymorphisms. J. Periodontol. 76, 49–56. doi: 10.1902/jop.2005.76.1.49
Schonfeld, S. E. (2010). Strategies for managing periodontal inflammation. J. Calif Dent. Assoc. 38, 272–283. doi: 10.1080/19424396.2010.12221789
Schulz, S., Immel, U. D., Just, L., Schaller, H. G., Gläser, C., Reichert, S. (2016). Epigenetic characteristics in inflammatory candidate genes in aggressive periodontitis. Hum. Immunol. 77, 71–75. doi: 10.1016/j.humimm.2015.10.007
Schwab, J. M., Serhan, C. N. (2006). Lipoxins and new lipid mediators in the resolution of inflammation. Curr. Opin. Pharmacol. 6, 414–420. doi: 10.1016/j.coph.2006.02.006
Sczepanik, F. S. C., Grossi, M. L., Casati, M., Goldberg, M., Glogauer, M., Fine, N., et al. (2020). Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way. Periodontol 2000 84, 45–68. doi: 10.1111/prd.12342
Serhan, C. N. (2005). Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot. Essent. Fatty Acids 73, 141–162. doi: 10.1016/j.plefa.2005.05.002
Shapira, L., Wilensky, A., Kinane, D. F. (2005). Effect of genetic variability on the inflammatory response to periodontal infection. J. Clin. Periodontol. 32, 72–86. doi: 10.1111/j.1600-051X.2005.00810.x
Shen, H., Guan, Q., Zhang, X., Yuan, C., Tan, Z., Zhai, L., et al. (2020). New mechanism of neuroinflammation in Alzheimer's disease: The activation of NLRP3 inflammasome mediated by gut microbiota. Prog. Neuropsychopharmacol. Biol. Psychiatry 100, 109884. doi: 10.1016/j.pnpbp.2020.109884
Slots, J. (2020). Primer on etiology and treatment of progressive/severe periodontitis: A systemic health perspective. Periodontol 2000 83, 272–276. doi: 10.1111/prd.12325
Sordi, M. B., Magini, R. S., Panahipour, L., Gruber, R. (2021). Pyroptosis-mediated periodontal disease. Int. J. Mol. Sci. 23, 372. doi: 10.3390/ijms23010372
Sousa, L. H., Linhares, E. V., Alexandre, J. T., Lisboa, M. R., Furlaneto, F., Freitas, R., et al. (2016). Effects of atorvastatin on periodontitis of rats subjected to glucocorticoid-induced osteoporosis. J. Periodontol. 87, 1206–1216. doi: 10.1902/jop.2016.160075
Stout-Delgado, H. W., Cho, S. J., Chu, S. G., Mitzel, D. N., Villalba, J., El-Chemaly, S., et al. (2016). Age-dependent susceptibility to pulmonary fibrosis is associated with NLRP3 inflammasome activation. Am. J. Respir. Cell Mol. Biol. 55, 252–263. doi: 10.1165/rcmb.2015-0222OC
Su, X., Guo, W., Yuan, B., Wang, D., Liu, L., Wu, X., et al. (2021). Artesunate attenuates bone erosion in rheumatoid arthritis by suppressing reactive oxygen species via activating p62/Nrf2 signaling. BioMed. Pharmacother. 137, 111382. doi: 10.1016/j.biopha.2021.111382
Suárez, L. J., Garzón, H., Arboleda, S., Rodríguez, A. (2020). Oral dysbiosis and autoimmunity: from local periodontal responses to an imbalanced systemic immunity. A Review. Front. Immunol. 11. doi: 10.3389/fimmu.2020.591255
Surlin, P., Lazar, L., Sincar, C., Gheorghe, D. N., Popescu, D. M., Boldeanu, V. M., et al. (2021). NLRP3 inflammasome expression in gingival crevicular fluid of patients with periodontitis and chronic hepatitis C. Mediators Inflamm. 2021, 6917919. doi: 10.1155/2021/6917919
Tang, T., Lang, X., Xu, C., Wang, X., Gong, T., Yang, Y., et al. (2017). CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation. Nat. Commun. 8, 202. doi: 10.1038/s41467-017-00227-x
Tegegne, B. A., Kebede, B. (2022). Probiotics, their prophylactic and therapeutic applications in human health development: A review of the literature. Heliyon. 8, e09725. doi: 10.1016/j.heliyon.2022.e09725
Van Ravensteijn, M. M., Timmerman, M. F., Brouwer, E. A. G., Slot, D. E. (2022). The effect of omega-3 fatty acids on active periodontal therapy: A systematic review and meta-analysis. J. Clin. Periodontol. 49, 1024–1037. doi: 10.1111/jcpe.13680
Wang, Y., Andrukhov, O., Rausch-Fan, X. (2017). Oxidative stress and antioxidant system in periodontitis. Front. Physiol. 8. doi: 10.3389/fphys.2017.00910
Wang, Z., Feng, X., Zhang, G., Li, H., Zhou, F., Xie, Y., et al. (2023). Artesunate ameliorates ligature-induced periodontitis by attenuating NLRP3 inflammasome-mediated osteoclastogenesis and enhancing osteogenic differentiation. Int. Immunopharmacol. 123, 110749. doi: 10.1016/j.intimp.2023.110749
Wang, Q., Guo, W. Y., Liu, L. L., Tao, X. Y., Lin, N., Kong, X. Y., et al. (2022). Inhibitory effect of artesunate on bone destruction in rheumatoid arthritis: an exploration based on AhR/ARNT/NQO1 signaling pathway. Zhongguo Zhong Yao Za Zhi. 47, 2698–2704. doi: 10.19540/j.cnki.cjcmm.20220110.401
Xiong, Y., Mi, B. B., Lin, Z., Hu, Y. Q., Yu, L., Zha, K. K., et al. (2022). The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity. Mil Med. Res. 9, 65. doi: 10.1186/s40779-022-00426-8
Yang, K., Xu, S., Zhao, H., Liu, L., Lv, X., Hu, F., et al. (2021). Hypoxia and Porphyromonas gingivalis-lipopolysaccharide synergistically induce NLRP3 inflammasome activation in human gingival fibroblasts. Int. Immunopharmacol. 94, 107456. doi: 10.1016/j.intimp.2021.107456
Ye, T., Tao, W. Y., Chen, X. Y., Jiang, C., Di, B., Xu, L. L. (2023). Mechanisms of NLRP3 inflammasome activation and the development of peptide inhibitors. Cytokine Growth Factor Rev. 74, 1–13. doi: 10.1016/j.cytogfr.2023.09.007
Ye, J., Xie, C., Wang, C., Huang, J., Yin, Z., Heng, B. C., et al. (2021). Promoting musculoskeletal system soft tissue regeneration by biomaterial-mediated modulation of macrophage polarization. Bioact Mater. 6, 4096–4109. doi: 10.1016/j.bioactmat.2021.04.017
Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C., Chen, X. (2021). Pyroptosis: mechanisms and diseases. Signal Transduct Target Ther. 6, 128. doi: 10.1038/s41392-021-00507-5
Zahid, A., Li, B., Kombe, A. J. K., Jin, T., Tao, J. (2019). Pharmacological inhibitors of the NLRP3 inflammasome. Front. Immunol. 10. doi: 10.3389/fimmu.2019.02538
Zamri, F., de Vries, T. J. (2020). Use of TNF inhibitors in rheumatoid arthritis and implications for the periodontal status: for the benefit of both? Front. Immunol. 11. doi: 10.3389/fimmu.2020.591365
Zang, Y., Song, J. H., Oh, S. H., Kim, J. W., Lee, M. N., Piao, X., et al. (2020). Targeting NLRP3 inflammasome reduces age-related experimental alveolar bone loss. J. Dent. Res. 99, 1287–1295. doi: 10.1177/0022034520933533
Zhang, J. (2020). The osteoprotective effects of artemisinin compounds and the possible mechanisms associated with intracellular iron: A review of in vivo and in vitro studies. Environ. Toxicol. Pharmacol. 76, 103358. doi: 10.1016/j.etap.2020.103358
Zhang, L., Duan, M., Pu, X., Zheng, H., Ning, X., Tu, Y., et al. (2024). GroEL triggers NLRP3 inflammasome activation through the TLR/NF-κB p-p65 axis in human periodontal ligament stem cells. Acta Biochim. Biophys. Sin. (Shanghai) 56, 1340–1351. doi: 10.3724/abbs.2024050
Zhang, X., He, S., Lu, W., Lin, L., Xiao, H. (2021). Glycogen synthase kinase-3β (GSK-3β) deficiency inactivates the NLRP3 inflammasome-mediated cell pyroptosis in LPS-treated periodontal ligament cells (PDLCs). In Vitro Cell Dev. Biol. Anim. 57, 404–414. doi: 10.1007/s11626-021-00583-5
Zhao, P., Liu, J., Pan, C., Pan, Y. (2014). NLRP3 inflammasome is required for apoptosis of Aggregatibacter actinomycetemcomitans-infected human osteoblastic MG63 cells. Acta Histochem. 116, 1119–1124. doi: 10.1016/j.acthis.2014.05.008
Zhao, Y., Quan, Y., Lei, T., Fan, L., Ge, X., Hu, S. (2022). The role of inflammasome NLPR3 in the development and therapy of periodontitis. Int. J. Med. Sci. 19, 1603–1614. doi: 10.7150/ijms.74575
Keywords: inflammation, immune response, pyroptosis, inflammasome, periodontal disease
Citation: López-Valverde N, Quispe-López N and Blanco Rueda JA (2024) Inflammation and immune response in the development of periodontal disease: a narrative review. Front. Cell. Infect. Microbiol. 14:1493818. doi: 10.3389/fcimb.2024.1493818
Received: 09 September 2024; Accepted: 14 November 2024;
Published: 29 November 2024.
Edited by:
Tim Schmitter, Symrise AG, GermanyReviewed by:
Irina Miralda, Emory University, United StatesCopyright © 2024 López-Valverde, Quispe-López and Blanco Rueda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Nansi López-Valverde, bmxvdmFsaGVyQHVzYWwuZXM=