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14 pages, 6123 KiB  
Article
Effects of Near-Infrared Diode Laser Irradiation on Pain Relief and Neuropeptide Markers During Experimental Tooth Movement in the Periodontal Ligament Tissues of Rats: A Pilot Study
by Kanako Okazaki, Ayaka Nakatani, Ryo Kunimatsu, Isamu Kado, Shuzo Sakata, Hirotaka Kiridoshi and Kotaro Tanimoto
Int. J. Mol. Sci. 2025, 26(15), 7404; https://doi.org/10.3390/ijms26157404 - 31 Jul 2025
Viewed by 158
Abstract
Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin [...] Read more.
Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), contribute to the transmission and maintenance of inflammatory pain. Heat shock protein (HSP) 70 plays a protective role against various stresses, including orthodontic forces. This study aimed to examine the effects of diode laser irradiation on neuropeptides and HSP 70 expression in periodontal tissues induced by experimental tooth movement (ETM). For inducing ETM for 24 h, 50 g of orthodontic force was applied using a nickel–titanium closed-coil spring to the upper left first molar and the incisors of 20 male Sprague Dawley rats (7 weeks old). The right side without ETM treatment was considered the untreated control group. In 10 rats, diode laser irradiation was performed on the buccal and palatal sides of the first molar for 90 s with a total energy of 100.8 J/cm2. A near-infrared (NIR) laser with a 808 nm wavelength, 7 W peak power, 560 W average power, and 20 ms pulse width was used for the experiment. We measured the number of facial groomings and vacuous chewing movements (VCMs) in the ETM and ETM + laser groups. Immunohistochemical staining of the periodontal tissue with SP, CGRP, and HSP 70 was performed. The number of facial grooming and VCM periods significantly decreased in the ETM + laser group compared to the ETM group. Moreover, the ETM + laser group demonstrated significant suppression of SP, CGRP, and HSP 70 expression. These results suggest that the diode laser demonstrated analgesic effects on ETM-induced pain by inhibiting SP and CGRP expression, and decreased HSP 70 expression shows alleviation of cell damage. Thus, although further validation is warranted for human applications, an NIR diode laser can be used for reducing pain and neuropeptide markers during orthodontic tooth movement. Full article
(This article belongs to the Special Issue Advances in Photobiomodulation Therapy)
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16 pages, 1855 KiB  
Article
Emodin-Loaded Thermoresponsive Hydrogel as a Potential Drug Delivery System for Periodontal Disease in a Rat Model of Ligature-Induced Periodontitis
by Gyu-Yeon Shim, Seong-Hee Moon, Seong-Jin Shin, Hyun-Jin Kim, Seunghan Oh and Ji-Myung Bae
Polymers 2025, 17(15), 2108; https://doi.org/10.3390/polym17152108 - 31 Jul 2025
Viewed by 197
Abstract
Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis [...] Read more.
Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article
(This article belongs to the Section Smart and Functional Polymers)
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20 pages, 1220 KiB  
Systematic Review
The Evolving Role of Stem Cells in Oral Health and Regeneration: A Systematic Review
by Gianna Dipalma, Grazia Marinelli, Arianna Fiore, Liviana Balestriere, Claudio Carone, Silvio Buongiorno, Francesco Inchingolo, Giuseppe Minervini, Andrea Palermo, Angelo Michele Inchingolo and Alessio Danilo Inchingolo
Surgeries 2025, 6(3), 65; https://doi.org/10.3390/surgeries6030065 - 30 Jul 2025
Viewed by 302
Abstract
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing [...] Read more.
Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article
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18 pages, 2540 KiB  
Article
Anti-Inflammatory, Antioxidant, and Reparative Effects of Casearia sylvestris Leaf Derivatives on Periodontium In Vitro
by Angélica L. R. Pavanelli, Maria Eduarda S. Lopes, André T. Reis, Flávio A. Carvalho, Sven Zalewski, André G. dos Santos, Joni A. Cirelli, James Deschner and Andressa V. B. Nogueira
Antioxidants 2025, 14(8), 901; https://doi.org/10.3390/antiox14080901 - 23 Jul 2025
Viewed by 333
Abstract
Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed [...] Read more.
Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article
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16 pages, 1668 KiB  
Article
Vitamin D3 Modulates Inflammatory and Antimicrobial Responses in Oral Epithelial Cells Exposed to Periodontitis-Associated Bacteria
by Fadime Karaca, Susanne Bloch, Fabian L. Kendlbacher, Christian Behm, Christina Schäffer and Oleh Andrukhov
Int. J. Mol. Sci. 2025, 26(14), 7001; https://doi.org/10.3390/ijms26147001 - 21 Jul 2025
Viewed by 283
Abstract
The oral epithelium is essential for maintaining oral health and plays a key role in the onset and progression of periodontitis. It serves as both a mechanical and immunological barrier and possesses antimicrobial activity. Vitamin D3, a hormone with known immunomodulatory [...] Read more.
The oral epithelium is essential for maintaining oral health and plays a key role in the onset and progression of periodontitis. It serves as both a mechanical and immunological barrier and possesses antimicrobial activity. Vitamin D3, a hormone with known immunomodulatory functions, may influence oral epithelial responses. This study investigated the effects of two vitamin D3 metabolites on key immunological and antimicrobial functions of oral epithelial cells, both under basal conditions and during bacterial challenge. Ca9-22 oral epithelial cells were treated with 1,25(OH)2D3 or 25(OH)D3 in the presence or absence of Tannerella forsythia, Fusobacterium nucleatum, or Porphyromonas gingivalis. Inflammatory responses were assessed by measuring gene and protein expression of IL-1β and IL-8. Antimicrobial activity was evaluated via expression of LL-37, hBD-2, and hBD-3, as well as direct bacterial killing assays. Expression of epithelial integrity markers E-cadherin and ICAM-1 was also analyzed. Vitamin D3 metabolites reduced IL-8 expression and significantly increased LL-37 expression and production in Ca9-22 cells. Both forms enhanced antimicrobial activity against all tested pathogens and modulated epithelial integrity markers. Vitamin D3 positively regulates antimicrobial and barrier functions in oral epithelial cells, suggesting a potential role in supporting oral health and preventing periodontitis progression. Full article
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16 pages, 3066 KiB  
Article
TLR4 Asp299Gly SNP (rs4986790) Protects from Periodontal Inflammatory Destruction by Altering TLR4 Susceptibility to LPS Stimulation
by Franco Cavalla, Claudia C. Biguetti, Ariadne Letra, Renato M. Silva, Alexandre R. Vieira, Franz J. Strauss and Gustavo P. Garlet
Biology 2025, 14(7), 894; https://doi.org/10.3390/biology14070894 - 21 Jul 2025
Viewed by 299
Abstract
Periodontitis is a multifactorial disease linked to host immune response and genetic predisposition. The TLR4 Asp299Gly single-nucleotide polymorphism (SNP, rs4986790) has been associated with altered responses to bacterial lipopolysaccharide (LPS) and may influence susceptibility to inflammatory diseases. Given the central role of TLR4 [...] Read more.
Periodontitis is a multifactorial disease linked to host immune response and genetic predisposition. The TLR4 Asp299Gly single-nucleotide polymorphism (SNP, rs4986790) has been associated with altered responses to bacterial lipopolysaccharide (LPS) and may influence susceptibility to inflammatory diseases. Given the central role of TLR4 in innate immune recognition of periodontal pathogens, this study investigates the role of rs4986790 in modulating susceptibility to periodontal inflammatory destruction. A total of 1410 individuals from four populations were genotyped, with findings indicating a significant protective effect of the polymorphic allele. Functional assays demonstrated enhanced IL-8 secretion and increased sensitivity to CD14 inhibition in cells expressing the variant receptor. These results suggest that rs4986790 modifies the LPS response via TLR4, potentially offering protection against periodontal breakdown. Full article
(This article belongs to the Section Genetics and Genomics)
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17 pages, 2234 KiB  
Article
Impact of Live Ligilactobacillus salivarius CCFM1332 and Its Postbiotics on Porphyromonas gingivalis Colonization, Alveolar Bone Resorption and Inflammation in a Rat Model of Periodontitis
by Qing Hong, Yu Ren, Xin Tang, Bingyong Mao, Qiuxiang Zhang, Jianxin Zhao, Shumao Cui and Zhenmin Liu
Microorganisms 2025, 13(7), 1701; https://doi.org/10.3390/microorganisms13071701 - 20 Jul 2025
Viewed by 435
Abstract
Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and [...] Read more.
Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and mechanisms of different forms of probiotics, including live bacteria and postbiotics, on periodontitis, we first screened and identified Ligilactobacillus salivarius CCFM1332 (L. salivarius CCFM1332) through in vitro antibacterial and anti-biofilm activity assays. Subsequently, we investigated its therapeutic potential in a rat model of experimental periodontitis. The results demonstrated that both live L. salivarius CCFM1332 (PL) and its postbiotics (PP) significantly reduced the gingival index (GI) and probing depth (PD) in rats, while suppressing oral colonization of P. gingivalis. Serum pro-inflammatory cytokine levels were differentially modulated: the PL group exhibited reductions in interleukin-17A (IL-17A), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by 39.31% (p < 0.01), 17.26% (p < 0.05), and 14.74% (p < 0.05), respectively, whereas the PP group showed decreases of 34.79% (p < 0.05), 29.85% (p < 0.01), and 19.74% (p < 0.05). Micro-computed tomography (Micro-CT) analysis demonstrated that compared to the periodontitis model group (PM), the PL group significantly reduced alveolar bone loss (ABL) by 30.1% (p < 0.05) and increased bone volume fraction (BV/TV) by 49.5% (p < 0.01). In contrast, while the PP group similarly decreased ABL by 32.7% (p < 0.05), it resulted in a 40.4% improvement in BV/TV (p > 0.05). Histological assessments via hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining confirmed that both the PL group and the PP group alleviated structural damage to alveolar bone-supporting tissues and reduced osteoclast-positive cell counts. This study suggests that live L. salivarius CCFM1332 and its postbiotics reduce alveolar bone resorption and attachment loss in rats through antibacterial and anti-inflammatory pathways, thereby alleviating periodontal inflammation in rats. Full article
(This article belongs to the Section Medical Microbiology)
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16 pages, 2408 KiB  
Article
Female Mice Lacking LSD1 in Myeloid Cells Are Resistant to Inflammatory Bone Loss
by Kristina Astleford-Hopper, Flavia Saavedra, Peter Bittner-Eddy, Clara Stein, Jennifer Auger, Rachel Clark, Juan E. Abrahante Llorens, Bryce A. Binstadt, Vivek Thumbigere-Math and Kim C. Mansky
Cells 2025, 14(14), 1111; https://doi.org/10.3390/cells14141111 - 19 Jul 2025
Viewed by 360
Abstract
Osteoclasts, which are derived from myeloid precursors, are essential for physiologic bone remodeling but also mediate pathological bone loss in inflammatory diseases such as periodontitis and rheumatoid arthritis. Lysine-specific demethylase (LSD1/KDM1A) is a histone demethylase that modulates the chromatin landscape via demethylation of [...] Read more.
Osteoclasts, which are derived from myeloid precursors, are essential for physiologic bone remodeling but also mediate pathological bone loss in inflammatory diseases such as periodontitis and rheumatoid arthritis. Lysine-specific demethylase (LSD1/KDM1A) is a histone demethylase that modulates the chromatin landscape via demethylation of H3K4me1/2 and H3K9me1/2, thereby regulating the expression of genes essential for deciding cell fate. We previously demonstrated that myeloid-specific deletion of LSD1 (LSD1LysM-Cre) disrupts osteoclast differentiation, leading to enhanced BV/TV under physiological conditions. In this study, we show that LSD1LysM-Cre female mice are similarly resistant to inflammatory bone loss in both ligature-induced periodontitis and K/BxN serum-transfer arthritis models. Bulk RNA-seq of mandibular-derived preosteoclasts from LSD1LysM-Cre mice with ligature-induced periodontitis revealed the upregulation of genes involved in inflammation, lipid metabolism, and immune response. Notably, LSD1 deletion blocked osteoclastogenesis even under TGF-β and TNF co-stimulation, which is an alternative RANKL-independent differentiation pathway. Upregulation of Nlrp3, Hif1α, and Acod1 in LSD1LysM-Cre preosteoclasts suggests that LSD1 is essential for repressing inflammatory and metabolic programs that otherwise hinder osteoclast commitment. These findings establish LSD1 as a critical epigenetic gatekeeper integrating inflammatory and metabolic signals to regulate osteoclast differentiation and bone resorption. Therapeutic inhibition of LSD1 may selectively mitigate inflammatory bone loss while preserving physiological bone remodeling. Full article
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17 pages, 1937 KiB  
Article
Detection of Protein Carbonylation in Gingival Biopsies from Periodontitis Patients with or Without Diabetes Mellitus—A Pilot Study
by Alexandra Efthymiou, Pinelopi Anastasiadou, Eleftherios Anagnostou, George Koliakos, Sotirios Kalfas and Ioannis Vouros
Dent. J. 2025, 13(7), 328; https://doi.org/10.3390/dj13070328 - 18 Jul 2025
Viewed by 844
Abstract
Background: Protein carbonylation is an irreversible post-translational modification that is considered indicative of oxidative damage. Objective: The purpose of the study was to examine by an immunohistochemical method for the first time the extent and localization of protein carbonylation in biopsies of gingiva [...] Read more.
Background: Protein carbonylation is an irreversible post-translational modification that is considered indicative of oxidative damage. Objective: The purpose of the study was to examine by an immunohistochemical method for the first time the extent and localization of protein carbonylation in biopsies of gingiva from periodontitis patients with or without diabetes mellitus (DM). Methods: These were processed for immunohistochemical staining of the carbonylated proteins, using the ENVISIOM FLEX Mini Kit, high pH, and anti-dinitrophenyl (DNP) antibody, a marker of oxidative damage to a given protein. The extent of protein carbonylation was semi-quantitatively estimated and evaluated by calculation of the Allred score (percentage of stained cells × intensity of staining). Results: The biopsies from periodontitis patients with diabetes mellitus (DM) exhibited higher staining scores as per the percentage of positively stained cells than the biopsies from patients with only periodontitis (means of 49.2 and 16.7, respectively), the difference being statistically significant (p = 0.036). The same trend was observed in the case of the combination of the above with the intensity of staining (score parameter) as well (means of 59.6 and 20.8, p = 0.036, respectively). Conclusions: An immunohistochemical method with the novelty of utilization for the first time of the anti-dinitrophenyl (DNP) antibody in gingival tissues was introduced and showed efficacy in detecting protein carbonylation indicative of oxidative stress and its impact in the pathogenesis of these two prevalent diseases of periodontitis and diabetes mellitus. Full article
(This article belongs to the Section Oral Hygiene, Periodontology and Peri-implant Diseases)
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16 pages, 1025 KiB  
Review
Periodontal Pathobionts and Respiratory Diseases: Mechanisms of Interaction and Implications for Interdisciplinary Care
by Byeongguk Kim and Nana Han
Biomedicines 2025, 13(7), 1741; https://doi.org/10.3390/biomedicines13071741 - 16 Jul 2025
Viewed by 494
Abstract
Periodontitis is a prevalent chronic inflammatory disease that has been increasingly recognized for its systemic impacts, including its connection to respiratory diseases such as pneumonia, chronic obstructive pulmonary disease (COPD), Obstructive Sleep Apnea (OSA), asthma, lung cancer, and COVID-19. This review explores the [...] Read more.
Periodontitis is a prevalent chronic inflammatory disease that has been increasingly recognized for its systemic impacts, including its connection to respiratory diseases such as pneumonia, chronic obstructive pulmonary disease (COPD), Obstructive Sleep Apnea (OSA), asthma, lung cancer, and COVID-19. This review explores the potential role of periodontal pathobionts, particularly Porphyromonas gingivalis (Pg), Treponema denticola (Td), Fusobacterium nucleatum (Fn), Aggregatibacter actinomycetemcomitans (Aa), and Tannerella forsythia (Tf), in respiratory health. These pathobionts contribute to respiratory diseases by facilitating pathogen adhesion, inducing epithelial cell apoptosis, and promoting inflammation. The review also highlights the beneficial effects of periodontal treatment in reducing pathobiont burden and systemic inflammation, thereby mitigating the risk of respiratory complications. This interdisciplinary approach underscores the need to consider oral health as a critical component in managing and preventing respiratory diseases, with future research needed to further clarify these associations and develop targeted interventions. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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16 pages, 4472 KiB  
Article
Effect of Low-Level Laser Therapy on Periodontal Host Cells and a Seven-Species Periodontitis Model Biofilm
by Selma Dervisbegovic, Susanne Bloch, Vera Maierhofer, Christian Behm, Xiaohui Rausch-Fan, Andreas Moritz, Christina Schäffer and Oleh Andrukhov
Int. J. Mol. Sci. 2025, 26(14), 6803; https://doi.org/10.3390/ijms26146803 - 16 Jul 2025
Viewed by 322
Abstract
Low-level laser therapy (LLLT) is gaining attention as an effective adjunct to non-surgical periodontal treatment. This study evaluates the potential of LLLT to reduce bacterial load in a clinically relevant in vitro subgingival biofilm model and its impact on the inflammatory response. A [...] Read more.
Low-level laser therapy (LLLT) is gaining attention as an effective adjunct to non-surgical periodontal treatment. This study evaluates the potential of LLLT to reduce bacterial load in a clinically relevant in vitro subgingival biofilm model and its impact on the inflammatory response. A subgingival biofilm model consisting of seven bacterial species was established. Primary human gingival fibroblasts (GFs) and periodontal ligament cells (PDLs) were cultured. Both biofilms and host cells were treated with the DenLase Diode Laser (980 nm) under various clinically relevant settings. The composition and structure of the seven-species biofilms were evaluated using quantitative PCR and fluorescence microscopy, respectively. The inflammatory response in host cells was analyzed by measuring the gene and protein expression levels of various inflammatory mediators. Laser treatment at power outputs ranging from 0.3 to 2 W had no significant effect on biofilm composition or architecture. LLLT, particularly at higher power settings, reduced the viability in both GFs and PDLs up to 70%. Gene expression levels of inflammatory mediators were only minimally influenced by laser treatment. However, LLLT significantly decreased the secretion of all examined cytokines. These findings suggest that LLLT with a 980 nm diode laser, under clinically relevant conditions, exerts anti-inflammatory rather than antimicrobial effects. Full article
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28 pages, 1081 KiB  
Review
The Role of Cytokines in Orthodontic Tooth Movement
by Hideki Kitaura, Fumitoshi Ohori, Aseel Marahleh, Jinghan Ma, Angyi Lin, Ziqiu Fan, Kohei Narita, Kou Murakami and Hiroyasu Kanetaka
Int. J. Mol. Sci. 2025, 26(14), 6688; https://doi.org/10.3390/ijms26146688 - 11 Jul 2025
Cited by 1 | Viewed by 455
Abstract
A challenge in orthodontic treatment is the long time taken to move teeth, which extends the long treatment period. Accordingly, various treatment protocols and orthodontic materials have been developed to shorten the orthodontic treatment period. However, controlling biological reactions is considered necessary to [...] Read more.
A challenge in orthodontic treatment is the long time taken to move teeth, which extends the long treatment period. Accordingly, various treatment protocols and orthodontic materials have been developed to shorten the orthodontic treatment period. However, controlling biological reactions is considered necessary to further shorten this treatment period. Orthodontic force results in compression of the periodontal ligament in the direction of tooth movement, resulting in various reactions in the periodontal ligament that induce osteoclast development, alveolar bone absorption, and teeth movement. The aforementioned reactions include immune reactions. Cytokines are substances responsible for intercellular communication and are involved in various physiological actions, including immune and inflammatory reactions. They cause various cellular responses, including cell proliferation, differentiation, cell death, and functional expression. Various cytokines are involved in biological reactions during orthodontic tooth movement (OTM). It is important to understand the role of cytokines during OTM in order to elucidate their biological response. This review discusses the role of cytokines during OTM. Full article
(This article belongs to the Special Issue Regulatory Network of Bone Metabolism)
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20 pages, 2742 KiB  
Review
Therapeutic Potential of Proanthocyanidins in Dentistry: A Focus on Periodontal Disease and on Dental Implants in Osteoporotic Patients
by Yoshimi Niwano, Shunichi Shishido, Midori Shirato, Hidetsugu Kohzaki and Keisuke Nakamura
Antioxidants 2025, 14(7), 850; https://doi.org/10.3390/antiox14070850 - 10 Jul 2025
Viewed by 513
Abstract
Proanthocyanidins (PACs), also called condensed tannins, are oligomers or polymers composed of flavan-3-ols. This review aimed to explore the potential role of PACs in ameliorating oral health problems, with a particular focus on their effects within the intestine—especially the colon, where most orally [...] Read more.
Proanthocyanidins (PACs), also called condensed tannins, are oligomers or polymers composed of flavan-3-ols. This review aimed to explore the potential role of PACs in ameliorating oral health problems, with a particular focus on their effects within the intestine—especially the colon, where most orally ingested PACs are believed to accumulate. Previous studies suggest that PACs can be beneficial in periodontal disease as well as in the osseointegration of dental implants in patients with osteoporosis. Periodontal disease is worsened by lipopolysaccharides (LPS) that enter the bloodstream due to disrupted tight junctions of intestinal epithelial cells, along with inflammatory cytokines released by activated macrophages. A similar mechanism is thought to affect osseointegration: LPS-induced inflammatory cytokines originating in the intestine can enter the bloodstream, contributing to bone loss and impaired integration of dental implants. PACs absorbed by intestinal epithelial cells can function as prooxidants, triggering the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which strengthens the gut barrier. This enhanced barrier reduces the levels of LPS and inflammatory cytokines in the blood, leading to the alleviation of periodontal inflammation and increased alveolar bone density, thereby promoting better osseointegration of dental implants. Full article
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17 pages, 3961 KiB  
Article
Therapeutic Potential of Local Application of Fibroblast Growth Factor-2 to Periodontal Defects in a Preclinical Osteoporosis Model
by Shinta Mori, Sho Mano, Naoki Miyata, Tasuku Murakami, Wataru Yoshida, Kentaro Imamura and Atsushi Saito
Bioengineering 2025, 12(7), 748; https://doi.org/10.3390/bioengineering12070748 - 9 Jul 2025
Viewed by 436
Abstract
This study investigated the effects of local fibroblast growth factor (FGF)-2 application on periodontal healing in an osteoporotic model, both in vivo and in vitro. Wistar rats were divided into the ovariectomy (OVX) and Control groups. Periodontal defects were created 8 weeks post-OVX [...] Read more.
This study investigated the effects of local fibroblast growth factor (FGF)-2 application on periodontal healing in an osteoporotic model, both in vivo and in vitro. Wistar rats were divided into the ovariectomy (OVX) and Control groups. Periodontal defects were created 8 weeks post-OVX and treated with hydroxypropylcellulose (HPC) or FGF-2 + HPC. Healing was evaluated through micro-computed tomography and histological analyses at 2 and 4 weeks. In vitro, bone marrow mesenchymal stromal cells (BMSCs) were cultured with/without FGF-2 and assessed for cell morphology, viability/proliferation, and osteoblastic marker expression. Alkaline phosphatase (ALP) staining was also performed. FGF-2-treated defects in both groups showed significantly greater bone volume fraction, trabecular number, and thickness compared to HPC only. Histologically, FGF-2 enhanced new bone formation, with the greatest levels in the Control group. In vitro, OVX BMSCs showed reduced actin staining versus controls. FGF-2 increased cell viability/proliferation and protrusions in both groups while downregulating Alpl and Bglap expression levels and reducing ALP-positive cells. FGF-2 increased new bone formation in the OVX group, stimulated proliferation of OVX BMSCs, and modulated their differentiation. FGF-2 could enhance periodontal healing even under osteoporotic conditions, albeit to a lesser extent. Full article
(This article belongs to the Special Issue Recent Advances in Periodontal Tissue Engineering)
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29 pages, 2331 KiB  
Review
Therapeutic Potential of Tanshinones in Osteolytic Diseases: From Molecular and Cellular Pathways to Preclinical Models
by Rafael Scaf de Molon
Dent. J. 2025, 13(7), 309; https://doi.org/10.3390/dj13070309 - 9 Jul 2025
Viewed by 494
Abstract
Tanshinones are a class of lipophilic diterpenoid quinones extracted from Salvia miltiorrhiza (Dan shen), a widely used herb in traditional Chinese medicine. These compounds, particularly tanshinone IIA (T-IIA) and sodium tanshinone sulfonate (STS), have been acknowledged for their broad spectrum of biological activities, [...] Read more.
Tanshinones are a class of lipophilic diterpenoid quinones extracted from Salvia miltiorrhiza (Dan shen), a widely used herb in traditional Chinese medicine. These compounds, particularly tanshinone IIA (T-IIA) and sodium tanshinone sulfonate (STS), have been acknowledged for their broad spectrum of biological activities, including anti-inflammatory, antioxidant, anti-tumor, antiresorptive, and antimicrobial effects. Recent studies have highlighted the potential of tanshinones in the treatment of osteolytic diseases, characterized by excessive bone resorption, such as osteoporosis, rheumatoid arthritis, and periodontitis. The therapeutic effects of tanshinones in these diseases are primarily attributed to their ability to inhibit osteoclast differentiation and activity, suppress inflammatory cytokine production (e.g., tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6), and modulate critical signaling pathways, including NF-kB, MAPK, PI3K/Akt, and the RANKL/RANK/OPG axis. Additionally, tanshinones promote osteoblast differentiation and mineralization by enhancing the expression of osteogenic markers such as Runx2, ALP, and OCN. Preclinical models have demonstrated that T-IIA and STS can significantly reduce bone destruction and inflammatory cell infiltration in arthritic joints and periodontal tissues while also enhancing bone microarchitecture in osteoporotic conditions. This review aims to provide a comprehensive overview of the pharmacological actions of tanshinones in osteolytic diseases, summarizing current experimental findings, elucidating underlying molecular mechanisms, and discussing the challenges and future directions for their clinical application as novel therapeutic agents in bone-related disorders, especially periodontitis. Despite promising in vitro and in vivo findings, clinical evidence remains limited, and further investigations are necessary to validate the efficacy, safety, and pharmacokinetics of tanshinones in human populations. Full article
(This article belongs to the Special Issue New Perspectives in Periodontology and Implant Dentistry)
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