Preventive effects of systemic Pistacia eurycarpa Yalt. administration on alveolar bone loss and oxidative stress in rats with experimental periodontitis.

OBJECTIVE: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. METHODOLOGY: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. RESULTS: Although the IL-1ß, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). CONCLUSION: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.

Integrated microbiome and metabolomics revealed the protective effect of baicalin on alveolar bone inflammatory resorption in aging.

BACKGROUND: With the growing aging population and longer life expectancy, periodontitis and tooth loss have become major health concerns. The gut microbiota, as a key regulator in bone homeostasis, has gathered immense interest. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis Georgi, has shown antioxidant and anti-inflammatory activities. PURPOSE: This study investigated, for the first time, the protective mechanism of baicalin against alveolar bone inflammatory resorption in aging mice by regulating intestinal flora and metabolites, as well as intestinal barrier function. METHODS: A ligature-induced periodontitis model was established in d-galactose (D-gal)-induced aging mice, and baicalin was administered at different dosages for 13 weeks. Body weight was measured weekly. The antioxidant and anti-inflammatory activity of baicalin were evaluated using serum superoxide dismutase (SOD), malonaldehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. The immune capability was assessed by thymus and spleen indices. Histopathological changes were observed in the heart, liver, ileum, and periodontal tissues. Alveolar bone absorption of maxillary second molars was examined, and osteoclasts were counted by tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, fecal samples were analyzed using 16S rRNA sequencing and non-targeted metabolomics to identify differences in intestinal bacterial composition and metabolites. RESULTS: Baicalin exhibited anti-aging properties, as evidenced by increased SOD activity and decreased levels of MDA, IL-6, and TNF-α in serum compared to the control group. Baicalin also ameliorated alveolar bone loss in the d-gal-induced aging-periodontitis group (p < 0.05). Furthermore, baicalin restored ileal permeability by up-regulating the expression of ZO-1 and occludin in aging-periodontitis groups (p < 0.05). Alpha diversity analysis indicated that baicalin-treated mice harbored a higher diversity of gut microbe. PCoA and ANOSIM results revealed significant dissimilarity between groups. The Firmicutes/Bacteroidetes (F/B) ratio, which decreased in periodontitis mice, was restored by baicalin treatment. Additionally, medium-dosage baicalin promoted the production of beneficial flavonoids, and enriched short-chain fatty acids (SCFAs)-producing bacteria. CONCLUSION: Intestinal homeostasis is a potential avenue for treating age-related alveolar bone loss. Baicalin exerts anti-inflammatory, antioxidant, and osteo-protective properties by regulating the gut microbiota and metabolites.

Preventive effects of Capparis Spinose extract on experimental periodontitis in rats: a histopathological and biochemical study.

This study aimed to assess the effectiveness of Capparis Spinose (CS) in preventing the initiation and progression of experimental periodontitis and to evaluate the effect of its on systemic oxidative stress in rats by experimental periodontitis model. Twenty-four male rats were equally divided into; Ligatured (L), non-ligatured (NL), and Ligatured with CS (11 days/day per 20 mg/kg) (LC) groups. Experimental periodontitis was induced with the silk suture technic. Alveolar bone loss was examined, and total antioxidant capacity(TAOC), total oxidant status(TOS), and oxidative stress index(OSI) were analyzed in rat serum. Although; alveolar bone loss showed statistically significant lower values in the LC group compared to L (p < 0.05), not NL. In the LC group, osteoclast and osteoblast numbers were statistically significant compared to L, but there were no statistical differences between LC and NL. Serum TAOC levels were significantly lower in group L compared to others and also LC group showed significant differences from NL. TOS and OSI levels were significantly higher in group L than in other groups. Within the limitation of the present study, it can be said that the destruction via local inflammation that may occur after the experimental periodontitis can be prevented by using CS.

Electroacupuncture regulates macrophage, neutrophil, and oral microbiota to alleviate alveolar bone loss and inflammation in experimental ligature-induced periodontitis.

AIM: Electroacupuncture (EA) regulates distant body physiology through somatic sensory autonomic reflexes, balances the microbiome, and can promote the release of immune cells into bloodstream, thereby inhibiting severe systemic inflammation. This makes it possible to use EA as an integrated treatment for periodontitis. MATERIALS AND METHODS: In this study, EA was applied to the ST36 acupoints in a ligature-induced periodontitis (LIP) mouse model. Then the effects of EA on periodontal myeloid cells, cytokines, and the microbiome were comprehensively analysed using flow cytometry, quantitative Polymerase Chain Reaction (PCR), and 16 S sequencing. RESULTS: Results demonstrated that EA could significantly relieve periodontal bone resorption. EA also suppressed the infiltration of macrophages and neutrophils, reduced gene expression of the pro-inflammatory cytokines IL-1ß, IL-6, IL-17 and TNF-α, and increased expression of the anti-inflammatory factors IL-4 and IL-10 in periodontal tissues. Moreover, composition of the periodontal microbiome was regulated by EA, finding that complex of microbiota, including supragingival Veillonella, subgingival Streptococcus, and subgingival Erysipelatoclostridium, were significantly reduced. Meanwhile, nitrate and nitrate-related activities of subgingival microbiota were reversed. Network analysis revealed close relationships among Veillonella, Streptococcus, and Bacteroides. CONCLUSIONS: Our study indicates that EA can effectively alleviate inflammation and bone resorption in LIP mice, potentially via the regulation of myeloid cells, cytokines, and periodontal microbiome.

Pharmacological Therapies for the Management of Inflammatory Bone Resorption in Periodontal Disease: A Review of Preclinical Studies.

Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host's immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal ligament, cementum, and alveolar bone, which lead to a wide range of disabilities and poor quality of life, thus imposing significant burdens. This process depends on the differentiation and activity of osteoclasts, the cells responsible for reabsorbing the bone tissue. Therefore, the inhibition of differentiation or activity of these cells is a promising strategy for controlling bone resorption. Several pharmacological drugs that target osteoclasts and inflammatory cells with immunomodulatory and anti-inflammatory effects, such as bisphosphonates, anti-RANK-L antibody, strontium ranelate, cathepsin inhibitors, curcumin, flavonoids, specialized proresolving mediators, and probiotics, were already described to manage inflammatory bone resorption during experimental PD progression in preclinical studies. Meantime, a growing number of studies have described the beneficial effects of herbal products in inhibiting bone resorption in experimental PD. Therefore, this review summarizes the role of several pharmacological drugs used for PD prevention and treatment and highlights the targeted action of all those drugs with antiresorptive properties. In addition, our review provides a timely and critical appraisal for the scientific rationale use of the antiresorptive and immunomodulatory medications in preclinical studies, which will help to understand the basis for its clinical application.

Oral Microbiome Using Colocasia antiquorum var. esculenta Extract Varnish in a Mouse Model with Oral Gavage of P. gingivalis ATCC 53978.

Background and Objective: There is increasing interest in preventing periodontitis using natural products. The purpose of this study was to investigate the effect of Colocasia antiquorum var. esculenta (CA) varnish on the oral microbiome and alveolar bone loss in a mouse periodontitis model. Materials and Methods: Antibacterial activity against Porphyromonas gingivalis (P. gingivalis) ATCC 53978 and cell cytotoxicity using CCK-8 on L929 cells were measured. Balb/c mice were assigned into five groups (negative control, positive control, CA in drinking water, varnish, and CA varnish). P. gingivalis was administered to the mice by oral gavage three times. After sacrifice, the oral microbiome and the levels of the inflammatory cytokine IL-1ß and matrix metalloproteinase-9 were analyzed. Alveolar bone loss was measured using micro-computed tomography. Results: CA extract showed an antibacterial effect against P. gingivalis (p < 0.05) and showed no cytotoxicity at that concentration (p > 0.05). Although alpha diversity of the oral microbiome did not statistically differ between the groups (p > 0.05), the relative abundance of dominant bacteria tended to be different between the groups. The inflammatory cytokine IL-1ß was reduced in the CA varnish group (p < 0.05), and no difference was observed in MMP-9 expression and alveolar bone loss (p > 0.05). Conclusions: CA varnish did not affect the overall microflora and exhibited an anti-inflammatory effect, suggesting that it is possibility a suitable candidate for improving periodontitis.

Synergistic Effect of Omega-3 and Probiotic Supplementation on Preventing Ligature-Induced Periodontitis.

Omega-3 and probiotics were shown to improve periodontal health by modulating the host immune response. Recently, the combination of omega-3 and probiotics has been shown to have a potential synergistic effect on host modulation. The aim of this study was to evaluate the prophylactic role of an omega-3 and probiotic combination on alveolar bone loss (ABL) via inflammatory response in an experimental periodontitis model. Forty-three rats were divided into 5 groups as control (C, n = 8), periodontitis (P, n = 8), omega-3 + periodontitis (O, n = 8), probiotic + periodontitis (Pro, n = 10), and omega-3 + probiotic + periodontitis (OPro, n = 9). Additionally to a standardized diet, omega-3 and/or probiotics were supplemented with oral gavage to the O, Pro, and OPro groups for 44 days. Periodontitis was induced by ligature to the P, O, Pro, and OPro groups on the 30th day for 2 weeks. ABL levels were measured histopathologically, and serum interleukin (IL) 1ß, IL6, and IL10 levels were analysed by enzyme-linked immunosorbent assay. ABL increased in all periodontitis groups (P, O, Pro, and OPro), compared to C group. Compared to P group, all oral gavage groups (O, Pro, and OPro) revealed decreased ABL, which was lowest in OPro group. IL1ß and IL6 decreased and IL10 increased in OPro group, compared to P group. In conclusion, prophylactic administration of omega-3 and probiotic combination reduced ABL and improved serum IL1ß, IL6, and IL10 levels more than their single use.

Moringa oleifera Lam. leaf extract safely inhibits periodontitis by regulating the expression of p38α/MAPK14-OPG/RANKL.

Periodontitis is a chronic disease clinically defined by loss of alveolar bone and connective tissue degeneration. Although Moringa oleifera Lam. (MO), a tree belonging to the Moringacea family, is widely used as an anti-inflammatory agent, its effect on periodontitis is still unclear. In this work, the phenol compounds in MO leaf extract (MOL) were identified by UPLC-ESI-MS/MS, and the anti-periodontitis effects and mechanism of MOL were predicted using network pharmacology and molecular docking. Moreover, the cytotoxic, antioxidant, and anti-periodontitis properties of MOL were confirmed in vivo and in vitro. In total, 88 phenolic compounds and 234 potential MOL periodontitis targets were screened, involving 2916 biological processes (BP). The p38α MAPK (MAPK14) pathway and OPG/RANKL complex were predicted to be involved in the process of molecular docking. Furthermore, experimental validation suggested that MOL significantly ameliorated inflammation and reduced alveolar bone resorption. The OPG/RANKL ratio was regulated through the inhibition of MAPK14, and the anti-periodontitis effect was realized by the antioxidant properties of MOL. Hematoxylin and eosin (H&E) staining of rat vital organs and the survival rate of RAW 264.7 cells confirmed the safety of MOL. The present study provides valuable insights into how MOL reduces inflammation and alveolar bone resorption associated with periodontitis. In conclusion, MOL safely inhibits chronic periodontitis highly likely by regulating the expression of p38α/MAPK14-OPG/RANKL. Network pharmacology coupled with experimental validation is an effective way to find new drugs in the future. DATA AVAILABILITY STATEMENT: The original data presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.

Berberine suppresses bone loss and inflammation in ligature-induced periodontitis through promotion of the G protein-coupled estrogen receptor-mediated inactivation of the p38MAPK/NF-κB pathway.

OBJECTIVE: This study aimed to explore the protective actions of berberine on inflammation, and alveolar bone loss in ligature-induced periodontitis, as well as its mechanism of action METHODS: Micro-computed tomography was conducted to analyze the alveolar bone loss, and hematoxylin and eosin staining was carried out to observe the histopathological changes and inflammation status. Furthermore, enzyme linked immunosorbent assay (ELISA) was conducted to evaluate the levels of TNF-α, IL-1ß, and IL-10, as well as western blots to determine the levels of GPR30 and the activity of the p38MAPK/NF-κB pathway. RESULTS: Berberine distinctly suppressed alveolar bone loss and inflammation in rats exposed to ligature-induced periodontitis. As well as this, berberine significantly decreased the levels of phosphorylated p38MAPK and phosphorylated NF-κB 65 through upregulating the GRP30 protein levels, this protective effects of berberine were reversed by injection of G15, along with the upregulated activity of the p38MAPK/NF-κB pathway in rats with periodontitis. CONCLUSIONS: Berberine had a clear inhibitory effect on alveolar bone loss and inflammation in rats exposed to ligature-induced periodontitis, and its putative mechanism of action was attributed to the downregulation of the activity of the P38MAPK/NF-κB pathway, mediated by the G Protein-coupled estrogen receptor.

SIRT1/FOXO3a axis plays an important role in the prevention of mandibular bone loss induced by 1,25(OH)2D deficiency.

It has been reported that 1,25 dihydroxyvitamin D [1,25(OH)2D] deficiency leads to the loss of mandibular bone, however the mechanism is unclear. We investigated whether the Sirt1/FOXO3a signaling pathway is involved in this process. Using a 1,25(OH)2D deficiency model induced by genetic deletion in mice of 25-hydroxyvitamin D-1α hydroxylase [1α(OH)ase-/- mice]. We first documented a sharp reduction of expression levels of Sirt1 in the 1α(OH)ase-/- mice in vivo. Next, we demonstrated dose-dependent upregulation of Sirt1 by treatment with exogenous 1,25(OH)2D3in vitro. We then identified a functional VDR binding site in the Sirt1 promoter. By crossing Prx1-Sirt1 transgenic mice with 1α(OH)ase-/- mice we demonstrated that the overexpression of Sirt1 in mesenchymal stem cells (MSCs) greatly improved the 1α(OH)ase-/- mandibular bone loss phenotype by increasing osteoblastic bone formation and reducing osteoclastic bone resorption. In mechanistic studies, we showed, in 1α(OH)ase-/- mice, decreases of Sirt1 and FoxO3a, an increase in oxidative stress as reflected by a reduction of the antioxidant enzymes peroxiredoxin1 (Prdx1), SOD1 and SOD2 expression, and an increase of markers for osteocyte senescence and senescence associated secretory phenotypes (SASP), including ß-galactosidase (ß-gal), p16, p53 and p21. The targeted overexpression of Sirt1 in the 1α(OH)ase-/- mice restored the expression levels of these molecules. Finally, we demonstrated that a Sirt1 agonist can upregulate FOXO3a activity by increasing deacetylation and nuclear translocation. Overall, results from this study support the concept that targeted increases in Sirt1/FOXO3a signaling levels can greatly improve the bone loss caused by 1,25(OH)2D deficiency.

Effect of low level laser therapy on crestal bone levels around dental implants-A pilot study.

BACKGROUND: Implant success is affected by initial bone resorption at the implant surface. Continuous efforts have been made to reduce the peri-implant crestal bone loss. Limited information is available regarding the influence of low level laser therapy (LLLT) on interaction between the bone and implant surface. PURPOSE: The aim of this pilot study was to assess the effect of LLLT on peri-implant crestal bone levels. MATERIALS AND METHODS: Twenty implants were placed in 20 patients who were randomly assigned to two groups. Group I patients' received no adjunctive treatment and group II patients' were administered LLLT using 980 nm diode laser at 0.1 W output power following implant placement. The energy density of 4 J/cm2 was delivered at six sites for a duration of 10 seconds per site. Crestal bone levels were evaluated primarily using digital intraoral periapical (IOPA) radiograph. The measurements were made immediately (T0) and 6 weeks (T1) post implant placement; and 6 months (T2) and 1 year (T3) post prosthetic loading time intervals and compared using repeated measures ANOVA test. RESULTS: Crestal bone levels at baseline were statistically not significant between groups (P = .880). At T3 time interval, the mean change in crestal bone levels around all anatomical implant sites measured was 0.81 (SE 0.04) mm for irradiated group and 0.97 (SE 0.04) mm for nonirradiated group. Intergroup analysis revealed statistically significant (P = .020) less crestal bone loss in group that received LLLT. CONCLUSION: Under the conditions of this study, LLLT reduced the crestal bone resorption surrounding dental implants. TRIAL REGISTRATION: The present clinical trial was not registered.

A semi-synthetic flavonoid from Bauhinia pulchella stem attenuates inflammatory osteolysis in periodontitis in rats: Impact on cytokine levels, oxidative stress, and RANK/RANKL/OPG pathway.

OBJECTIVES: Many species of theBauhinia genus have been widely used in folk medicine as analgesic, anti-inflammatory and antioxidant agents. (-)-Fisetinidol palmitate is a semi-syntetic flavonoid obtained from the ethanolic extract of the stem of Bauhinia pulchella. This study aimed to evaluate the antiresorptive effect of the semi-syntetic (-)-fisetinidol palmitate in ligature-induced periodontitis in rats. Also, it evaluated the mechanism of action of (-)-fisetinidol palmitate and its toxicity. DESIGN: Periodontitis was inducedvia a nylon thread ligature (3.0) around the second upper left molars. Rats were treated (oral gavage) once a day for 11 days with (-)-fisetinidol palmitate (0.01 or 0.1 mg/kg) or saline vehicle. RESULTS: (-)-Fisetinidol palmitate (0.1 mg/kg) reduced alveolar bone loss, increased bone alkaline phosphatase (BALP), superoxide dismutase (SOD), and catalase (CAT) activity; also, it decreased IL1-ß, IL-8/CINC-1, nitrite/nitrate levels and myeloperoxidase activity. (-)-Fisetinidol palmitate reduced the mRNA levels of IL1-ß, IL-6, RANK, and RANK-L, while it increased the OPG ones. No statistical differences (P > 0.05) were observed in the transaminases (ALT, AST) and Total Alkaline Phosphatase (TALP) levels among groups. (-)- CONCLUSIONS: Fisetinidol palmitate did not result in any signs of toxicity and had anti-resorptive effects in a pre-clinical trial of periodontitis, showing antioxidant activity with the involvement of the RANK/RANKL/OPG pathway.

Bromelain reduces the non-alcoholic fatty liver disease and periodontal damages caused by ligature-induced periodontitis.

OBJECTIVE: The objective of this research was to evaluate the effects of bromelain (derived from Ananas comosus) upon periodontitis in rats. MATERIALS AND METHODS: Twenty-four rats were separated into groups: control, periodontitis, and bromelain treatment. Bromelain was administered daily by intraperitoneal injection for 20 days. Periodontitis was induced by ligature around the first molars. Oral parameters and blood biomarkers were measured. The histopathological evaluation of the hepatic tissue was performed. Bromelain treatment significantly reduced several oral inflammatory parameters, alveolar bone loss, and blood biomarkers compared to the rats on periodontitis. RESULTS: Treatment with bromelain improved the steatosis score. Bromelain used in ligature-induced periodontitis in rats was able to reduce the oral inflammatory parameters Gingival Bleeding Index (GBI), tooth mobility (TM), probing pocket depth (PPD), malondialdehyde (MDA), alveolar bone height (ABH) and gingival myeloperoxidase (MPO) and blood parameters (cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase). Bromelain treatment reduced the impact of periodontitis, such as the reduction of hepatic steatosis and improvement in the dosages of MDA and GSH. CONCLUSION: Bromelain acts as a potential adjunct in the non-surgical treatment of periodontitis and, consequently, reduces the impact of periodontitis, acting as anti-inflammatory and antioxidant.

The Influence of Local Pamidronate Application on Alveolar Dimensional Preservation after Tooth Extraction-An Animal Experimental Study.

The aim of this randomized, controlled animal exploratory trial was to investigate the influence of local application of aminobisphosphonate pamidronate during the socket preservation procedure. Mandibular premolars were extracted in five Göttingen minipigs. Two animals underwent socket preservation using BEGO OSS (n = 8 sockets) and three animals using BEGO OSS + Pamifos (15 mg) (n = 12 sockets). After jaw impression, cast models (baseline, eight weeks postoperative) were digitized using an inLab X5 scanner (Dentsply Sirona) and the generated STL data were superimposed and analyzed with GOM Inspect 2018 (GOM, Braunschweig). After 16 weeks, the lower jaws were prepared and examined using standard histological methods. In the test group (BEGO OSS + pamidronate), buccooral dimensional loss was significantly lower, both vestibulary (0.80 ± 0.57 mm vs. 1.92 ± 0.63 mm; p = 0.00298) and lingually (1.36 ± 0.58 mm vs. 2.56 ± 0.65 mm; p = 0.00104) compared with the control group (BEGO OSS). The test group showed a significant difference between vestibular and lingual dimensional loss (p = 0.04036). Histology showed cortical and cancellous bone in the alveolar sockets without signs of local inflammation. Adjuvant application of pamidronate during socket preservation reduces alveolar dimensional loss significantly. Further investigations with regard to dose-response relationships, volume effects, side effects, and a verification of the suitability in combination with other bone substitute materials (BSMs) are necessary.

Is low level laser therapy or ozone therapy more effective for bone healing? Understanding the mechanisms of HIF-1α, RANKL and OPG.

Periodontitis is a common chronic infection of dental tissues. Ozone therapy (OT) and low level laser therapy (LLLT) are useful treatments for periodontitis. We investigated the effects of OT and LLLT on periodontal disease-induced bone destruction in rats with experimentally induced periodontitis (EP). We used 30 male Wistar rats divided into three groups: control, OT and LLLT. EP was induced by placing a 3.0 silk suture around the cervix of the left mandibular first molar tooth. OT was performed using an ozone generator at 80% concentration. LLLT was applied using a diode laser. Both OT and LLLT were performed for two weeks at two day intervals. Histomorphometric and immunohistochemical analyses also were performed. Alveolar bone loss was significantly less in the LLLT group compared to the control group. The number of HIF-1α positive cells was significantly less in the LLLT group compared to the control group. We found significantly fewer RANKL-positive cells in the OT group compared to the control group. The number of osteoprotegerin (OPG) positive cells was significantly greater for the LLLT group than for the control group. Although both treatments produced positive effects, LLLT appears to be more effective for increasing alveolar bone formation.

Tanshinone prevents alveolar bone loss in ovariectomized osteoporosis rats by up-regulating phosphoglycerate dehydrogenase.

Osteoporosis is manifested by reduced bone mass. Tanshinone has been shown to affect osteoclast differentiation, but its role in osteoporosis remains less clear. This study aimed to investigate the effects and molecular mechanisms of tanshinone on osteoporosis. Osteoporosis was induced by bilateral ovariectomy (OVX) in adult female rats treated with or without tanshinone. Trabecular bone structure was assessed by micro-computed tomography (micro-CT). Bone marrow stromal cells (BMSCs) were isolated for analysis of stemness and senescence. mRNA levels of age related genes were examined and the role of the gene that was upregulated by tanshinone treatment was suppressed to determine its involvement in tanshinone mediated effects. Finally, the mechanism underlying tanshinone induced gene upregulation was explored. We found that tanshinone treatment restored alveolar bone structure in OVX rats as well as the stemness and senescence status of BMSCs isolated from OVX rats. Tanshinone upregulated Phgdh mRNA levels and inhibition of phosphoglycerate dehydrogenase Phgdh, the protein encoded by the Phgdh gene, abolished the effects of tanshinone on BMSC stemness and senescence. Finally, we found that OVX lead to hypermethylation of the promoter region of Phgdh which was suppressed by tanshinone treatment. Our study shows that tanshinone potently suppress OVX induced osteoporosis and BMSC senescence through upregulation of PHGDH.

Hydroxyl radicals generated by hydrogen peroxide photolysis recondition biofilm-contaminated titanium surfaces for subsequent osteoblastic cell proliferation.

Titanium dental implants have been successfully used for decades; however, some implants are affected by peri-implantitis due to bacterial infection, resulting in loss of supporting bone. This study aimed to evaluate the effect of an antimicrobial chemotherapy employing H2O2 photolysis-developed to treat peri-implantitis-on biofilm-contaminated titanium surfaces in association with osteoblastic cell proliferation on the treated surface. Titanium discs were sandblasted and acid-etched, followed by contamination with a three-species biofilm composed of Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mitis. This biofilm model was used as a simplified model of clinical peri-implantitis biofilm. The discs were subjected to ultrasound scaling, followed by H2O2 photolysis, wherein 365-nm LED irradiation of the disc immersed in 3% H2O2 was performed for 5 min. We analysed proliferation of mouse osteoblastic cells (MC3T3-E1) cultured on the treated discs. Compared with intact discs, biofilm contamination lowered cell proliferation on the specimen surface, whereas H2O2 photolysis recovered cell proliferation. Thus, H2O2 photolysis can recover the degraded biocompatibility of biofilm-contaminated titanium surfaces and can potentially be utilised for peri-implantitis treatment. However, to verify the findings of this study in relation to clinical settings, assessment using a more clinically relevant multi-species biofilm model is necessary.

Platycarya strobilacea leaf extract inhibits tumor necrosis factor-α production and bone loss induced by Porphyromonas gingivalis-derived lipopolysaccharide.

OBJECTIVE: Remodeling of alveolar bone is controlled by osteoclast-mediated bone resorption and osteoblast-induced bone formation. LPS of Porphyromonas gingivalis, a major causative agent of periodontitis, produces proinflammatory cytokines in host immune cells, which thereby triggers osteoclastogenesis and leads to alveolar bone resorption. We investigated the anti-periodontitis potential of Platycarya strobilacea leaf extract (PLE), which is used as a traditional medicine in Asian countries. DESIGN: TNF-α levels in cell culture media were measured using a commercially available enzyme-linked immunosorbent assay kit. Osteoclast differentiation was observed by tartrate-resistant acid phosphatase staining, and the expression levels of osteoclastogenic genes were measured by quantitative real-time PCR. Bone-resorbing activity was confirmed by the resorption pit formation, gelatin zymographic, and the cathepsin K activity assays. Osteogenic differentiation was confirmed with an ALP activity assay and alizarin red S staining. RESULTS: PLE treatment inhibited the production of TNF-α in P. gingivalis LPS-stimulated RAW264.7 macrophages. In bone marrow-derived macrophages serving as osteoclast precursors, PLE treatment blocked RANKL-induced osteoclastogenesis and gene expression levels of the osteoclastogenic transcription factor NFATc1, DC-STAMP for osteoclast fusion, and cathepsin K for osteoclast activity. In addition, PLE treatment reduced the formation of resorption pits and the secretion of MMP 9 and cathepsin K from the differentiated osteoclasts. Furthermore, PLE treatment induced osteogenesis by increasing ALP activity and calcium content in preosteoblastic cells. CONCLUSION: PLE inhibits P. gingivalis LPS-induced TNF-α production and bone resorption and induces bone formation. PLE may be a beneficial agent to promote oral health by inhibiting periodontitis-induced alveolar bone loss.

Effects of an ethanol extract from Lactobacillus paracasei subsp. paracasei NTU 101 fermented skimmed milk on lipopolysaccharide-induced periodontal inflammation in rats.

The increased incidence of periodontal disease in recent years has garnered considerable attention. Numerous studies have confirmed that probiotics, such as lactic acid bacteria, can ameliorate periodontal inflammation. The current study aimed to assess the effect of an ethanol extract of Lactobacillus paracasei subsp. paracasei NTU 101-fermented skimmed milk (NTU101FM) on lipopolysaccharide (LPS)-induced periodontal inflammation in rats. NTU101FM ethanol extract significantly ameliorated the weight loss caused by periodontal inflammation. NTU101FM ethanol extract treatment also reduced the oral microbial levels and decreased the levels of alveolar bone loss. Finally, NTU101FM ethanol extract was found to ameliorate periodontal inflammation by decreasing the levels of pro-inflammatory cytokines and reducing oxidative stresses induced by LPS. Overall, our findings demonstrate that NTU101FM ethanol extract could be developed as a functional food that could ameliorate periodontal inflammation.

Inhibitory Effect of Standardized Curcuma xanthorrhiza Supercritical Extract on LPS-Induced Periodontitis in Rats.

Periodontitis, which is a severe inflammatory disease caused by endotoxins secreted from oral pathogens, destructs gingival tissue and alveolar bone. Curcuma xanthorrhiza, commonly called Java turmeric, has been shown to possess anti-bacterial and anti-inflammatory activities. The present study evaluated the inhibitory effect of C. xanthorrhiza supercritical extract (CXS) standardized with xanthorrhizol on lipopolysaccharide (LPS)-induced periodontitis in an animal model. LPS was topically injected into the periodontium of Sprague-Dawley rats to induce periodontitis and CXS (30 and 100 mg·kg-1·day-1) was orally administered after day 12. Histologically, CXS inhibited the collapse of gingival tissue by preventing cell infiltration. CXS significantly downregulated the expression of matrix metalloproteases (MMPs) and inflammation-related biomarkers, such as nuclear factor-kappa B (NF-κB) and interleukin-1 beta (IL-1ß) in gingival tissue. CXS also improved bone remodeling by downregulating osteoclastic transcription factors, such as nuclear factor of activated T-cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K. In addition, CXS upregulated osteoblast differentiation-related markers, alkaline phosphate (ALP) and collagen type I alpha (COLA1). Thus, CXS can ameliorate periodontitis by inhibiting inflammation and improving bone remodeling.