SOST and DKK1 were upregulated in patients with CP presenting DM and/or smoking. DM, alone or with smoking, particularly influenced the correlations of SOST and DKK1 with each other and with the other biomarkers mostly at mRNA levels, as well as with periodontal pathogens.

The subgingival levels and prevalence of the bacterial species studied are not significantly different in subjects with chronic periodontitis presenting DM, smokers or smokers with DM. In addition, DM and smoking, jointly and individually, do not considerably affect the subgingival levels of target periodontal pathogens in patients with chronic periodontitis.

Background and objectives Strontium ranelate is a medication indicated for the treatment of osteoporosis that presents concomitant anti‐resorptive and osteoanabolic dual biological activity. However, the effects of strontium ranelate on alveolar bone have been poorly explored. Furthermore, to date, there are no data on the effects of this medication on alveolar bone loss (BL) during conditions of estrogen deficiency. Therefore, the aim of this study was to evaluate the effects of strontium ranelate on ligature‐induced periodontitis in estrogen‐deficient and estrogen‐sufficient rats. Methods Ninety‐six rats were assigned to one of the following groups: sham‐surgery + water (estrogen‐sufficient; n = 24); ovariectomy + water (estrogen‐deficient; n = 24), sham‐surgery + strontium ranelate (ranelate/estrogen‐sufficient; n = 24) and; ovariectomy + strontium ranelate (ranelate/estrogen‐deficient; n = 24). The rats received strontium ranelate or water from the 14th day after ovariectomy until the end of the experiment. On the 21st day after ovariectomy, one first mandibular molar received a ligature, while the contralateral tooth was left unligated. Eight rats per group were killed at 10, 20, and 30 days after ligature placement. Bone loss (BL) and trabecular bone area (TBA) were analyzed in the furcation area of ligated and unligated teeth at all experimental times by histometry. Tartrate‐resistant acid phosphatase (TRAP) positive cells and immunohistochemical staining for osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), and receptor activator of NF‐КB ligand (RANKL) were assessed in the ligated teeth at 30 days after ligature placement. Results At 10 and 30 days, ligated teeth of the estrogen‐deficient group exhibited higher BL, when compared to all other groups (P < .05). At 10 days, TBAs were higher in the unligated teeth of strontium ranelate‐treated groups, when compared to those of untreated groups (P < .05). At 30 days, the ligated teeth of the estrogen‐deficient group exhibited lower TBA than the other groups (P < .05). There were no differences among groups regarding the number of TRAP‐stained cells (P < .05). The strontium ranelate‐treated groups exhibited lower expressions of OCN and RANKL than the untreated groups (P < .05). The estrogen‐sufficient group presented higher staining for OPG than both treated and untreated estrogen‐deficient groups (P < .05). Conclusions Strontium ranelate prevented ligature‐induced BL in an estrogen‐deficiency condition and, to a certain extent, increased TBA in the presence and absence of periodontal collapse in states of estrogen deficiency and estrogen sufficiency. Furthermore, strontium ranelate also affected the expression of bone markers, appearing to have acted predominantly as an anti‐resorptive agent.

ObjectivesThis study evaluated the effects of type 2 diabetes mellitus (DM), smoking, and these two factors combined on gingival crevicular fluid levels and ratios of pro‐/anti‐inflammatory cytokines. Associations between cytokines with each other and with key periodontal pathogens in periodontal sites under the challenge of one or both of these risk factors were also assessed.MethodsA total of 102 subjects with periodontitis were included in this cross‐sectional study and assigned to one of the following groups: non‐diabetic non‐smokers (control group, n = 25), non‐smokers with DM (DM group, n = 30), non‐diabetic smokers (S group, n = 26), and smokers with DM (S + DM group, n = 21). The levels of 13 pro‐inflammatory (IFN‐γ, TNF‐α, MIP‐1α, GM‐CSF, IL‐1β, IL‐2, IL‐6, IL‐7, IL‐8, IL‐12, IL‐17, IL‐21, and IL‐23) and 5 anti‐inflammatory (IL‐4, IL‐5, IL‐10, IL‐13, and TGF‐β) cytokines were assessed in healthy and diseased sites, using multiplex immunoassay. Ratios of pro‐/anti‐inflammatory cytokines were obtained in all possible permutations. The levels of 7 key periodontal pathogens were evaluated by qPCR.ResultsOverall, the ratios of pro‐/anti‐inflammatory cytokines were higher in healthy and diseased sites of the DM group and in healthy sites of the S + DM group, and lower in diseased sites of the S group, compared with the control (p < .05). The proportion of the pro‐inflammatory cytokines in relation to the 18 cytokines studied was higher in the DM group and lower in the S group, whereas the proportion of the anti‐inflammatory cytokines was lower in both diabetic groups and higher in the S group, compared to the control (p < .05). A cluster of six common cytokines (IL‐4, IL‐5, IL‐12, IL‐13, IL‐21, and IL‐23) was observed in the diseased sites of all groups studied. Eight common cytokines (IL‐4, IL‐5, IL‐12, IL‐13, IL‐17, IL‐21, IL‐23, and IFN‐γ) grouped closely in the healthy sites of both diabetic groups. Significant associations between pathogens and cytokines occurred mainly in the diseased sites of the S + DM group (p < .05).ConclusionDiabetes mellitus induced an overall pro‐inflammatory state, while smoking mainly stimulated immunosuppression in periodontal sites. When the two risk factors overlapped, smoking seemed to partially assuage the hyperinflammatory effect of DM.

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Background: This study evaluated the impact of strontium ranelate on toothextraction wound healing in estrogen-deficient and estrogen-sufficient rats. Methods: Ninety-six Wistar rats (90 days of age) were allocated into one of the following groups: sham-surgery+water (estrogen-sufficient); ovariectomy+ water (estrogen-deficient), sham-surgery+strontium ranelate (625 mg/kg/d) (strontium/estrogen-sufficient); ovariectomy+strontium ranelate (625 mg/kg/d) (strontium/estrogen-deficient). Water or strontium ranelate were administrated from the 14th day post-ovariectomy/sham surgery until euthanasia. Maxillary first molars were extracted at 21 days after sham/ovariectomy surgery. Rats were euthanized at 10, 20, and 30 days post-extractions. The following parameters were analyzed inside tooth-extraction wound: proportion of newly formed bone (bone healing/BH), number of cells stained for tartrate-resistant acid phosphatase (TRAP) and immunohistochemical staining for five bone metabolism-related markers (osteocalcin [OCN], osteopontin [OPN], bone sialoprotein [BSP], osteoprotegerin [OPG] and receptor activator of NF-КB ligand [RANKL]). Results: The estrogen-deficient group presented lower BH than all other groups at 20 and 30 days post-extraction (P < 0.05). The number of TRAP-stained cells was higher in the estrogen-deficient group than in estrogen-sufficient group at 30 days post-extraction (P < 0.05). The strontium /estrogen-sufficient group exhibited stronger staining for OCN, when compared to the estrogen-sufficient and estrogen-deficient groups (P < 0.05). Both strontium ranelate-treated groups presented higher staining of OPN and BSP than both untreated groups (P < 0.05). The strontium/estrogen-sufficient group demonstrated stronger staining for OPG than the estrogen-deficient group (P < 0.05). The estrogen-sufficient group and both groups treated with strontium ranelate showed lower expression of RANKL than the estrogen-deficient group (P < 0.05).

The purpose of this investigation was to evaluate the effects of lithium chloride (LiCl) on the socket healing of estrogen-deficient rats. Seventy-two rats were allocated into one of the following groups: Control, Ovariectomy and LiCl (150 mg/kg/2 every other day orally) + Ovariectomy. Animals received LiCl or water from the 14th day post-ovariectomy, until the completion of the experiment. On the 21st day after ovariectomy, the first molars were extracted. Rats were euthanized on the 10th, 20th and 30th days following extractions. Bone healing (BH), TRAP positive cells and immunohistochemical staining for OPG, RANKL, BSP, OPN and OCN were evaluated. The Ovariectomy group presented decreased BH compared to the LiCl group at 10 days, and the lowest BH at 20 days (p<0.05). At 30 days, the Ovariectomy and LiCl-groups presented lower BH than that of the Control (p<0.05). The number of TRAP-stained cells was the lowest in the LiCl group at 20 days and the highest in the Ovariectomy group at 30 days (p<0.05). At 10 days of healing, the LiCl group demonstrated stronger staining for all bone markers when compared to the other groups, while the Ovariectomy group presented higher RANKL expression than that of the Control (p<0.05). LiCl enhanced bone healing in rats with estrogen deficiency, particularly in the initial healing phases. However, as data on the effects of lithium chloride on bone tissue are still preliminary, more studies related to its toxicity and protocol of administration are necessary before its application in clinical practice.