Artificial intelligence in dental education: ChatGPT's performance on the periodontic in-service examination.

BACKGROUND: ChatGPT's (Chat Generative Pre-Trained Transformer) remarkable capacity to generate human-like output makes it an appealing learning tool for healthcare students worldwide. Nevertheless, the chatbot's responses may be subject to inaccuracies, putting forth an intense risk of misinformation. ChatGPT's capabilities should be examined in every corner of healthcare education, including dentistry and its specialties, to understand the potential of misinformation associated with the chatbot's use as a learning tool. Our investigation aims to explore ChatGPT's foundation of knowledge in the field of periodontology by evaluating the chatbot's performance on questions obtained from an in-service examination administered by the American Academy of Periodontology (AAP). METHODS: ChatGPT3.5 and ChatGPT4 were evaluated on 311 multiple-choice questions obtained from the 2023 in-service examination administered by the AAP. The dataset of in-service examination questions was accessed through Nova Southeastern University's Department of Periodontology. Our study excluded questions containing an image as ChatGPT does not accept image inputs. RESULTS: ChatGPT3.5 and ChatGPT4 answered 57.9% and 73.6% of in-service questions correctly on the 2023 Periodontics In-Service Written Examination, respectively. A two-tailed t test was incorporated to compare independent sample means, and sample proportions were compared using a two-tailed χ2 test. A p value below the threshold of 0.05 was deemed statistically significant. CONCLUSION: While ChatGPT4 showed a higher proficiency compared to ChatGPT3.5, both chatbot models leave considerable room for misinformation with their responses relating to periodontology. The findings of the study encourage residents to scrutinize the periodontic information generated by ChatGPT to account for the chatbot's current limitations.

Extracellular Release of Citrullinated Vimentin Directly Acts on Osteoclasts to Promote Bone Resorption in a Mouse Model of Periodontitis.

Elevated osteoclast (OC)-mediated bone resorption, a common pathological feature between periodontitis and rheumatoid arthritis (RA), implicates a possible mutually shared pathogenesis. The autoantibody to citrullinated vimentin (CV), a representative biomarker of RA, is reported to promote osteoclastogenesis (OC-genesis). However, its effect on OC-genesis in the context of periodontitis remains to be elucidated. In an in vitro experiment, the addition of exogenous CV upregulated the development of Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear OCs from mouse bone marrow cells and increased the formation of resorption pits. However, Cl-amidine, an irreversible pan-peptidyl arginine deiminase (PAD) inhibitor, suppressed the production and secretion of CV from RANKL-stimulated OC precursors, suggesting that the citrullination of vimentin occurs in OC precursors. On the other hand, the anti-vimentin neutralizing antibody suppressed in vitro Receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced OC-genesis. The CV-induced upregulation of OC-genesis was abrogated by the Protein kinase C (PKC)-δ inhibitor Rottlerin, accompanied by the downmodulation of OC-genesis-related genes, including Osteoclast stimulatory transmembrane protein (OC-STAMP), TRAP and Matrix Metallopeptidase 9 (MMP9) as well as extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP)-kinase phosphorylation. Elevated levels of soluble CV and vimentin-bearing mononuclear cells were found in the bone resorption lesions of periodontitis induced in mice in the absence of an anti-CV antibody. Finally, local injection of anti-vimentin neutralizing antibody suppressed the periodontal bone loss induced in mice. Collectively, these results indicated that the extracellular release of CV promoted OC-genesis and bone resorption in periodontitis.

Optimizing teaching effectiveness in dental education for a new generation of learners.

PURPOSE: Today's dental students, Generation Z (Gen Z), are said to learn differently than those of previous generations. As generations of dental students vary, our teaching styles must keep up with unique and changing groups of individuals. METHODS: This article discusses learner-focused teaching methods including techniques that address the characteristics of Gen Z learners. Blended learning methods that combine online media with traditional face-to-face sessions, team-based learning, and a flipped classroom format have previously been suggested as ways to increase learning effectiveness and student satisfaction. RESULTS: In this paper, the characteristics and preferences of Gen Z students are described along with the challenges they create with conventional teaching methods. An implementation strategy using principles from organizational agility and Bolman and Deal's Four Frames Model is proposed for dental schools to transition to a more learner-centered teaching approach. CONCLUSIONS: The suggested strategy can be customized and could be useful to schools that wish to enhance their teaching methods to meet the learning needs of Gen Z dental students and beyond.

Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging.

Aging is associated with increased prevalence and severity of pathogenic outcomes of periodontal disease, including soft tissue degeneration and bone loss around the teeth. Although lipopolysaccharide (LPS) derived from the key periodontal pathogen Porphyromonas gingivalis (Pg) plays an important role in the promotion of inflammation and osteoclastogenesis via toll-like receptor (TLR)4 signaling, its pathophysiological role in age-associated periodontitis remains unclear. This study investigated the possible effects of Pg-LPS on RANKL-primed osteoclastogenesis and ligature-induced periodontitis in relation to aging using young (2 months old) and aged (24 months old) mice. To the best of our knowledge, our results indicated that expression of TLR4 was significantly diminished on the surface of osteoclast precursors isolated from aged mice compared with that of young mice. Furthermore, our data demonstrated that the TLR4 antagonist (TAK242) dramatically decreased the numbers of tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts differentiated from RANKL-primed young osteoclast precursors (OCPs) compared with those isolated from aged mice in response to Pg-LPS. In addition, using a ligature-induced periodontitis mouse model, we demonstrated that Pg-LPS elevated (1) secretion of senescence-associated secretory phenotype (SASP) markers, including the pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, as well as osteoclastogenic RANKL, and (2) the number of OCPs and TRAP+ osteoclasts in the periodontal lesion induced in young mice. In contrast, Pg-LPS had little, or no, effect on the promotion of periodontitis inflammation induced in aged mice. Altogether, these results indicated that periodontal disease in older mice occurs in a manner independent of canonical signaling elicited by the Pg-LPS/TLR4 axis.

Intravital endoscopic technology for real-time monitoring of inflammation caused in experimental periodontitis.

We report a novel method for in situ imaging of microvascular permeability in inflamed gingival tissue, using state-of-the-art Cellvizio™ intravital endoscopic technology and a mouse model of ligature-induced periodontitis. The silk ligature was first placed at the upper left second molar. Seven days later, the ligature was removed, and the animals were intravenously injected with Evans blue. Evans blue dye, which selectively binds to blood albumin, was used to monitor the level of inflammation by monitoring vascular permeability in control non-diseased and ligature-induced experimental periodontitis tissue. More specifically, leakage of Evans blue-bound albumin from the micro-capillary to connective tissue indicates the state of inflammation occurring in the specific site. Evans blue leakage from blood vessels was imaged in situ by directly attaching the endoscope (mini Z tip) of the Cellvizio™ system to the gingival tissue without any surgical incision. Evans blue emission intensity was significantly elevated in gingiva of periodontitis lesions, but not control non-ligature placed gingiva, indicating that this technology can be used as a potential minimally invasive diagnostic tool to monitor the level of inflammation at the periodontal disease site.

Correcting Mucogingival Deformities at the Time of Extraction for a Future Implant Site: A Case Report.

INTRODUCTION: Existing soft tissue deformities around a tooth planned for extraction and replacement with a dental implant may jeopardize the esthetic and physiologic outcome of any dental implant treatment. If soft tissue deformities can be prevented, minimized, or corrected at the time of tooth extraction for the future implant site and the adjacent teeth, more predictable outcomes with superior esthetics and health can be accomplished along with fewer surgical visits. CASE PRESENTATION: This case report describes a patient who presented with mucogingival deformities around a tooth scheduled for extraction and subsequent implant placement. The adjacent tooth also presented with similar characteristics. Surgical modifications and refinements were used by performing an epithelialized free gingival graft (E-FGG) at the time of tooth extraction to enhance the tissue quality of the future implant site and its neighboring tooth. CONCLUSION: The identification of inadequate attached gingiva in the area of future implant placement and neighboring teeth in the treatment planning phase can enable clinicians to address any mucogingival deformities with E-FGGs at the time of extraction without subjecting the patient to any additional surgical visits and healing time.

Expression profile of human gingival fibroblasts induced by interleukin-1beta reveals central role of nuclear factor-kappa B in stabilizing human gingival fibroblasts during inflammation.

BACKGROUND: Interleukin (IL)-1beta is a key cytokine in the pathogenesis of periodontitis, and it induces inflammatory mediators in periodontal diseases. We developed immortalized human gingival fibroblasts (HGFs), investigated the effects of IL-1beta on the gene expression using expression arrays containing approximately 40,000 genes, and tested the role of nuclear factor-kappa B (NF-kappaB) in maintaining an activated HGF population. METHODS: Total RNA was isolated from IL-1beta-induced and mock-induced control cells. Gene expression analyses were performed using expression arrays and confirmed by quantitative real-time polymerase chain reaction. Western blot analysis to show inhibitor of kappa B-alpha (IkappaBalpha) phosphorylation and immunostaining of cells for NF-kappaB nuclear translocation were performed. Apoptosis was confirmed by assay of poly ADP-ribose polymerase (PARP) cleavage. RESULTS: A total of 382 probe sets corresponding to 254 genes were differentially expressed in IL-1beta-induced cells (P <0.001). A total of 215 genes were upregulated, and 39 genes were downregulated. Most notable NF-kappaB pathway members (NFkappaB1, NFkappaB2, IkappaBalpha, IkappaBepsilon, IkappaBzeta, REL, RELB, and TA-NFKBH) were upregulated. IkappaBalpha was phosphorylated, and NF-kappaB accumulated in the nucleus. An IL-1beta-induced set of 27 genes was downregulated by an NF-kappaB inhibitor, leading to a decreased number of viable cells and suggesting an antiapoptotic role for NF-kappaB. CONCLUSIONS: IL-1beta leads to a large number of significant expression changes consistent with a pathologic role in periodontitis, including enhancement of inflammatory cytokines, chemokines, transcription factors, matrix metalloproteinases, adhesion molecules, and especially NF-kappaB-dependent antiapoptotic genes. NF-kappaB activation blocks apoptosis, thereby stabilizing the HGF population in inflammation.

Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip.

BACKGROUND: UV irradiation activates the epidermal growth factor receptor, induces Egr1 expression and promotes apoptosis in a variety of cell types. We examined the hypothesis that Egr1 regulates genes that mediate this process by use of a chip-on-chip protocol in human tumorigenic prostate M12 cells. RESULTS: UV irradiation led to significant binding of 288 gene promoters by Egr1. A major functional subgroup consisted of apoptosis related genes. The largest subgroup of 24 genes belongs to the epidermal growth factor receptor-signal transduction pathway. Egr1 promoter binding had a significant impact on gene expression of target genes. Conventional chromatin immunoprecipitation and quantitative real time PCR were used to validate promoter binding and expression changes. Small interfering RNA experiments were used to demonstrate the specific role of Egr1 in gene regulation. UV stimulation promotes growth arrest and apoptosis of M12 cells and our data clearly show that a downstream target of the epidermal growth factor receptor, namely Egr1, mediates this apoptotic response. Our study also identified numerous previously unknown targets of Egr1. These include FasL, MAX and RRAS2, which may play a role in the apoptotic response/growth arrest. CONCLUSIONS: Our results indicate that M12 cells undergo Egr1-dependent apoptotic response upon UV stimulation and led to the identification of downstream targets of Egr1, which mediate epidermal growth factor receptor function.

The effects of selective COX-2 inhibitor/celecoxib and omega-3 fatty acid on matrix metalloproteinases, TIMP-1, and laminin-5gamma2-chain immunolocalization in experimental periodontitis.

BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in tissue-destruction mechanisms-associated periodontitis. MMP-8 and -13 are the predominant collagenases that are important in the extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, whereas laminin-5 indicates basal membrane modification and epithelial induction. The purpose of the present study was to evaluate the effects of celecoxib and omega-3 fatty acid administration on the gingival tissue expression of MMP-8, -13, and -14, tissue inhibitor of MMP (TIMP)-1, and laminin (Ln)-5gamma2-chain in rat experimental periodontitis induced by Escherichia coli endotoxin (lipopolysaccharide [LPS]). METHODS: Experimental periodontitis was induced in rats by repeated LPS injection. Fifty-one adult male Sprague-Dawley rats were divided into six study groups: saline control, LPS, LPS + celecoxib, LPS + therapeutic omega-3 (TO3), prophylactic omega-3 + LPS + omega-3 (P+TO3), and LPS + celecoxib + omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given as a single agent or as combination therapy for 14 days. On day 15, all rats were sacrificed, and gingival tissues were analyzed immunohistochemically for the expression of MMP-8, -13, and -14, TIMP-1, and Ln-5gamma2-chain. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS: Alveolar bone loss was significantly higher in all study groups compared to the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline group (P = 0.001). Very low expression of MMP-8 was found in the celecoxib, P+TO3, and combination groups. TO3 increased TIMP-1 expression significantly compared to the LPS group (P <0.05). Individual celecoxib and P+TO3 administration increased MMP-14 significantly compared to saline control and LPS groups (P <0.05). No significant differences were found among the study groups with regard to Ln-5gamma2-chain and MMP-13 expressions (P >0.05). CONCLUSIONS: Selective cyclooxygenase-2 inhibitor, prophylactic omega-3 fatty acid, and a combination of these two agents can inhibit gingival tissue MMP-8 expression. Moreover, the individual administration of therapeutic omega-3 may increase gingival TIMP-1 expression in contrast to no effect on MMP-8, -13, and -14 expressions in experimental periodontitis. These experimental findings in a rat model of LPS-induced periodontitis need to be verified by clinical human studies.

Matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase-1, and laminin-5 gamma2 chain immunolocalization in gingival tissue of endotoxin-induced periodontitis in rats: effects of low-dose doxycycline and alendronate.

BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, and laminin (Ln)-5 is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP (TIMP)-1; and Ln-5 gamma2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats. METHODS: Experimental periodontitis was induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP-8, -13, and -14, Ln-5 gamma2 chain, and TIMP-1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS: Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP-8 compared to LPS (P = 0.01). Combined drug administration reduced MMP-14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln-5 gamma2 chain expression were found between the study groups (P >0.05). MMP-14 significantly correlated with the Ln-5 gamma2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03). CONCLUSIONS: Our findings suggest that alendronate and/or doxycycline may inhibit MMP-8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP-1 expression in gingiva. However, these effects of combined low-dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice.

Matrix Metalloproteinases, Tissue Inhibitor of Matrix Metalloproteinase-1, and Laminin-5 γ2 Chain Immunolocalization in Gingival Tissue of Endotoxin-Induced Periodontitis in Rats: Effects of Low-Dose Doxycycline and Alendronate.

BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, and laminin (Ln)-- is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP (TIMP)-1; and Ln-5 γ2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats. METHODS: Experimental periodontitis was induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP-8, -13, and -14, Ln-- γ2 chain, and TIMP-1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS: Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP-8 compared to LPS (P = 0.01). Combined drug administration reduced MMP-14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln-5 γ2 chain expression were found between the study groups (P >0.05). MMP-14 significantly correlated with the Ln-5 γ2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03). CONCLUSIONS: Our findings suggest that alendronate and/or doxycycline may inhibit MMP-8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP-1 expression in gingiva. However, these effects of combined low-dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice.

Dietary supplementation of omega-3 fatty acid and circulating levels of interleukin-1beta, osteocalcin, and C-reactive protein in rats.

BACKGROUND: In this study, we evaluated the effects of two different regimes of dietary supplementation of omega-3 fatty acid on serum levels of interleukin-1 beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS: Experimental periodontitis was induced by repeated injections of Escherichia coli lipopolysaccharide (LPS). Thirty-nine adult male Sprague-Dawley rats were divided into four study groups as follows: an LPS positive control group; a saline (negative) control group; and two different groups with omega-3 fatty acid dietary supplementation, one in which we gave the supplement subsequent to disease induction (TO3) and the other in which the agent was started prior to and continued subsequent to LPS injections (P + TO3). In the TO3 group, omega-3 fatty acid administration was performed for 14 days following induction of experimental periodontitis. In the P + TO3 group, omega-3 fatty acid was given for 14 days prior to the start of LPS injections and was continued for another 14 days subsequent to the induction of experimental periodontitis. On day 15 of the first LPS injection, serum samples were obtained and rats were sacrificed. Serum samples were analyzed for IL-1beta, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS: LPS injection resulted in statistically significantly more bone loss compared to the saline control group (P <0.05). None of the omega-3 fatty acid administration groups showed evidence that this fatty acid was effective in preventing LPS-induced alveolar bone loss. TO3 and P + TO3 groups revealed significantly higher IL-1beta and OC levels than the LPS group (P <0.05). The study groups exhibited no significant differences in the serum CRP levels. CONCLUSIONS: Omega-3 fatty acid administration does not seem to influence circulating levels of CRP. The significantly increased serum OC level observed in both omega-3 fatty acid regimes is curious and could have an effect on bone turnover, as could the further significant increase in serum IL-1beta, which could counteract any osteoblastic induction by OC through promotion of osteoclast activity. The lack of a therapeutic benefit of omega-3 fatty acid in this study, despite the effects on OC and IL-1beta, is difficult to explain, and further studies are required to more fully assess the potential role of this fatty acid in periodontal treatment.

Effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on serum interleukin-1beta, osteocalcin, and C-reactive protein levels in rats.

BACKGROUND: The aim of this study was to evaluate the effects of selective cyclooxygenase-2 inhibitor, celecoxib, and omega-3 fatty acid on serum levels of interleukin 1-beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS: Experimental periodontitis in rats was induced by repeated injection of purified lipopolysaccharide (LPS) derived from Escherichia coli endotoxin. Forty-seven adult male Sprague-Dawley rats were divided into five study groups as follows: saline control, LPS, LPS + celecoxib, LPS + omega-3 fatty acid, and LPS + celecoxib + omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given alone or in combination during 14 days of the experimental study period. At the end of the 2-week protocol, serum samples were obtained, and the rats were sacrificed. Serum samples were analyzed for IL-1beta, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS: According to the morphometric measurements, the LPS and drug treatment groups showed significantly higher bone loss than the saline control group (P <0.05). Omega-3 fatty acid, both alone and in combination with celecoxib, revealed significantly higher IL-1beta levels than LPS and celecoxib groups (P <0.05). Individual and combined administration of celecoxib and omega-3 fatty acid significantly increased OC levels compared to the LPS group (P <0.05). There were no significant differences in serum CRP levels. CONCLUSIONS: Celecoxib and/or omega-3 fatty acid administration does not significantly influence circulating levels of CRP. The significantly increased serum OC level observed after individual and combination administration suggests that celecoxib and omega-3 fatty acid may influence bone remodeling and thereby inhibit the progression of alveolar bone resorption. However, the failure to observe any significant inhibition of bone loss in celecoxib- and/or omega-3 fatty acid-treated rats compared to the LPS group suggests that their therapeutic effect may be reduced by other factors, such as increases in serum IL-1beta promoting osteoclast activity.

Effects of Selective Cyclooxygenase-2 Inhibitor and Omega-3 Fatty Acid on Serum Interleukin-1ß, Osteocalcin, and C-Reactive Protein Levels in Rats.

BACKGROUND: The aim of this study was to evaluate the effects of selective cyclooxygenase-2 inhibitor, celecoxib, and omega-3 fatty acid on serum levels of interleukin 1-beta (IL-1ß), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS: Experimental periodontitis in rats was induced by repeated injection of purified lipopolysaccharide (LPS) derived from Escherichia coli endotoxin. Forty-seven adult male Sprague-Dawley rats were divided into five study groups as follows: saline control, LPS, LPS + celecoxib, LPS + omega-3 fatty acid, and LPS + celecoxib + omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given alone or in combination during 14 days of the experimental study period. At the end of the 2-week protocol, serum samples were obtained, and the rats were sacrificed. Serum samples were analyzed for IL-1ß, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS: According to the morphometric measurements, the LPS and drug treatment groups showed significantly higher bone loss than the saline control group (P <0.05). Omega-3 fatty acid, both alone and in combination with celecoxib, revealed significantly higher IL-1ß levels than LPS and celecoxib groups (P <0.05). Individual and combined administration of celecoxib and omega-3 fatty acid significantly increased OC levels compared to the LPS group (P <0.05). There were no significant differences in serum CRP levels. CONCLUSIONS: Celecoxib and/or omega-3 fatty acid administration does not significantly influence circulating levels of CRP. The significantly increased serum OC level observed after individual and combination administration suggests that celecoxib and omega-3 fatty acid may influence bone remodeling and thereby inhibit the progression of alveolar bone resorption. However, the failure to observe any significant inhibition of bone loss in celecoxib- and/or omega-3 fatty acid-treated rats compared to the LPS group suggests that their therapeutic effect may be reduced by other factors, such as increases in serum IL-1ß promoting osteoclast activity.

Dietary Supplementation of Omega-3 Fatty Acid and Circulating Levels of Interleukin-1ß, Osteocalcin, and C-Reactive Protein in Rats.

BACKGROUND: In this study, we evaluated the effects of two different regimes of dietary supplementation of omega-3 fatty acid on serum levels of interleukin-1 beta (IL-1ß), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS: Experimental periodontitis was induced by repeated injections of Escherichia coli lipopolysaccharide (LPS). Thirty-nine adult male Sprague-Dawley rats were divided into four study groups as follows: an LPS positive control group; a saline (negative) control group; and two different groups with omega-3 fatty acid dietary supplementation, one in which we gave the supplement subsequent to disease induction (TO3) and the other in which the agent was started prior to and continued subsequent to LPS injections (P + TO3). In the TO3 group, omega-3 fatty acid administration was performed for 14 days following induction of experimental periodontitis. In the P + TO3 group, omega-3 fatty acid was given for 14 days prior to the start of LPS injections and was continued for another 14 days subsequent to the induction of experimental periodontitis. On day 15 of the first LPS injection, serum samples were obtained and rats were sacrificed. Serum samples were analyzed for IL-1ß, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS: LPS injection resulted in statistically significantly more bone loss compared to the saline control group (P <0.05). None of the omega-3 fatty acid administration groups showed evidence that this fatty acid was effective in preventing LPS-induced alveolar bone loss. TO3 and P + TO3 groups revealed significantly higher IL-1ß and OC levels than the LPS group (P <0.05). The study groups exhibited no significant differences in the serum CRP levels. CONCLUSIONS: Omega-3 fatty acid administration does not seem to influence circulating levels of CRP. The significantly increased serum OC level observed in both omega-3 fatty acid regimes is curious and could have an effect on bone turnover, as could the further significant increase in serum IL-1ß, which could counteract any osteoblastic induction by OC through promotion of osteoclast activity. The lack of a therapeutic benefit of omega-3 fatty acid in this study, despite the effects on OC and IL-1ß, is difficult to explain, and further studies are required to more fully assess the potential role of this fatty acid in periodontal treatment.

Systemic low-dose doxycycline and alendronate administration and serum interleukin-1beta, osteocalcin, and C-reactive protein levels in rats.

BACKGROUND: The aim of the present study was to evaluate the effects of systemic administration of low-dose doxycycline and a bisphosphonate, alendronate, on serum levels of interleukin-1beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis in rats. METHODS: Experimental periodontitis was induced by repeated injection of purified lipopolysaccharide (LPS) derived from Escherichia coli endotoxin. Forty-seven adult male Sprague-Dawley rats were divided into five study groups and given LPS, LPS + doxycycline, LPS + alendronate, LPS + doxycycline + alendronate, and saline control. At the end of the 1-week protocol, blood samples were obtained, and the rats were sacrificed. Serum samples were analyzed for IL-1beta, OC, and CRP concentrations by enzyme-linked immunosorbent assay (ELISA). The jaws were defleshed, and alveolar bone loss was assessed morphometrically. Data were evaluated statistically by non-parametric tests. RESULTS: Morphometric measurements revealed significantly more bone loss in the LPS group compared to the saline control group (P <0.05). Alendronate revealed slight inhibition on alveolar bone loss either alone or in combination with doxycycline (alveolar bone loss: 0.41 mm in alendronate and combined drug treatment groups versus 0.45 mm in LPS and doxycycline groups). Significantly higher IL-1beta levels were observed with alendronate either alone or in combination with doxycycline than in the LPS group (P <0.05). Combined administration of doxycycline and alendronate showed significantly higher levels of OC than all of the other groups (P <0.01). Serum CRP levels did not exhibit significant differences between the study groups. CONCLUSIONS: Alendronate either alone or in combination with doxycycline provided slight inhibition on LPS-induced alveolar bone resorption. The significantly increased serum OC level observed in the combined drug treatment group suggests that combined administration of alendronate and doxycycline might increase bone remodeling and thereby inhibit the progression of alveolar bone resorption in rats.