Alveolar Bone Mineral Research Articles

Differences in alveolar bone mineral density by tooth type in female osteoporotic patients treated with bisphosphonates

Differences in alveolar bone mineral density by tooth type in female osteoporotic patients treated with bisphosphonates

Alveolar bone healing patterns in chronic kidney failure and kidney transplant recipients: A pixel intensity and fractal analyses.

To assess and compare radiographically the alveolar bone after tooth extractions in individuals with chronic kidney failure undergoing hemodialysis (CKFh), those submitted to kidney transplantation (KT), and those without kidney disease (CG) by using fractal analysis (FA) and pixel intensity (PI). Periapical radiographs of 48 CKFh individuals (87 extracted teeth), 12 KT individuals (26 extracted teeth and 29 control individuals [76 extracted teeth] were analyzed at 7 and 60 days after tooth extraction. Fractal dimension (FD) and PI were assessed to evaluate the alveolar trabecular bone structural complexity and mineral content. The difference in FD values between the 7th and 60th postoperative days in KT individuals (0.03±0.08) was significantly lower compared to those of CKFh individuals (0.09±0.10) and controls (0.15±0.06). As for the difference in PI values, KT (4.55±10.24) and CKFh groups (9.88±15.90) showed significantly lower values compared to those of the control group (17.93±11.86) in the same period. These results indicate a lower gain in the trabecular bone complexity and bone density in the alveolus of KT individuals compared to the other groups. Overall mineral content and thickness of the bone in the plane of the x-ray beam were lower in KT and CKFh individuals compared to controls, reflecting the need for careful consideration in recommending rehabilitation with dental implants for these patients. Particular attention should be given to the potential challenges in oral rehabilitation of KT patients.

A persistent mineralization process in alveolar bone throughout the postnatal growth stage in rats

ObjectiveAlveolar bone quality is essential for the maxillofacial integrity and function, and depends on alveolar bone mineralization. This study aims to investigate the in vivo changes in alveolar bone mineralization, from the perspective of mineral deposition and crystal transition in postnatal rats. DesignNine postnatal time points of Wistar rats, ranging from day 1 to 56, were set to obtain the maxillary alveolar bone samples. Each time point consisted of ninety rats, with 45 females and 45 males. Macromorphology of alveolar bone was reconducted by Micro-Computed Tomography and the mineral content was quantified via Thermogravimetric analysis, Scanning Electron Microscope, High-Resolution Transmission Electron Microscopy and vibrational spectroscopy. Furthermore, the crystallinity and composition were characterized by vibrational spectroscopy, X-ray Diffraction, X-ray Photoelectron Spectroscopy and Selected Area Electron Diffraction. ResultsThe progressive increase of mineral deposition was accompanied by substantial growth in alveolar bone mass and volume in postnatal rats. Whereas the mineral percentage initially decreased and then increased, reaching a nadir on postnatal day 14 (P14) when tooth eruption was first observed. Besides, localized mineralization was initiated by the formation of amorphous precursors and then converted into mineral crystals, while there was no statistically significant change in the average crystallinity of the bone during growth. ConclusionMineralization of alveolar bone is ongoing throughout the early growth in postnatal rats. Mineral deposition increases with age, whereas the crystallinity remains stable within a certain range. Besides, the mineral percentage reaches its lowest point on P14, which may be attributed to tooth eruption.

A reliable deep-learning-based method for alveolar bone quantification using a murine model of periodontitis and micro-computed tomography imaging

Objectives: This study focuses on artificial intelligence (AI)-assisted analysis of alveolar bone for periodontitis in a mouse model with the aim to create an automatic deep-learning segmentation model that enables researchers to easily examine alveolar bone from micro-computed tomography (µCT) data without needing prior machine learning knowledge.Methods: Ligature-induced experimental periodontitis was produced by placing a small-diameter silk sling ligature around the left maxillary second molar. At 4, 7, 9, or 14 days, the maxillary bone was harvested and processed with a µCT scanner (µCT-45, Scanco). Using Dragonfly (v2021.3), we developed a 3D deep learning model based on the U-Net AI deep learning engine for segmenting materials in complex images to measure alveolar bone volume (BV) and bone mineral density (BMD) while excluding the teeth from the measurements.Results: This model generates 3D segmentation output for a selected region of interest with over 98 % accuracy on different formats of µCT data. BV on the ligature side gradually decreased from 0.87 mm3 to 0.50 mm3 on day 9 and then increased to 0.63 mm3 on day 14. The ligature side lost 4.6 % of BMD on day 4, 9.6 % on day 7, 17.7 % on day 9, and 21.1 % on day 14.Conclusions: This study developed an AI model that can be downloaded and easily applied, allowing researchers to assess metrics including BV, BMD, and trabecular bone thickness, while excluding teeth from the measurements of mouse alveolar bone.Clinical significance: This work offers an innovative, user-friendly automatic segmentation model that is fast, accurate, and reliable, demonstrating new potential uses of artificial intelligence (AI) in dentistry with great potential in diagnosing, treating, and prognosis of oral diseases.

Progesterone affects periodontitis in perimenopausal women and in an experimental rat model

Background/purposeProgesterone (PG) is sex steroid hormone that commonly used to control menopausal symptoms, but its exact role in periodontitis remains unclear. This study aimed to investigate the effects of PG on periodontitis in perimenopausal women and in an experimental rat model. Materials and methodsTotal 412 perimenopausal women with periodontitis and a history of PG deficiency-induced uterine dysfunctional bleeding were enrolled, among which 209 women had been treated with PG. The alveolar bone height (ABH) and bone mineral density (BMD) were measured by cone beam computed tomography in the full-mouth. Additionally, a ligation-induced rat model of periodontitis was established. After treated with PG, the alveolar bone was evaluated by micro-computed tomography, and the expression of osteogenic and inflammatory markers was evaluated by immunohistochemistry. The levels of inflammatory markers were further measured by enzyme linked immunosorbent assay. ResultsIn perimenopausal women with periodontitis, significantly lower maximum mesial ABH and higher minimum lingual/palatal BMD were revealed in the PG group than in the control group. Compared with the control group, the mean values of BMD around all teeth were significantly higher in the PG group. In a rat model of periodontitis, the intervention of PG significantly improved the quality of alveolar bone, up-regulated osteogenic markers, and down-regulated inflammatory markers. ConclusionPG is associated with the remission of alveolar bone loss in perimenopausal women with periodontitis. PG may contribute to the remission of periodontitis through inhibiting alveolar bone loss and inflammation.

Sex differences and age-related changes in the mandibular alveolar bone mineral density using a computer-aided measurement system for intraoral radiography

This study aimed to conduct a cross-sectional data analysis of the alveolar bone mineral density (al-BMD) in 225 patients of various ages and different sexes. The al-BMD value in the mandibular incisor region was calculated using a computer-aided measurement system (DentalSCOPE) for intraoral radiography. All participants with intact teeth (101 males and 124 females; age range, 25–89 years) were divided into three age-segregated groups (25–49, 50–74, and > 75 years). Statistical differences were evaluated using the Mann–Whitney U or Kruskal–Wallis test. Males exhibited significantly greater al-BMD than females (p < 0.001). The highest means were observed in the 25–49 age group, regardless of sex (1007.90 mg/cm2 in males, 910.90 mg/cm2 in females). A 9.8% decrease in al-BMD was observed with the increase in age in males (25–49 to 50–74 years; p = 0.004); however, no further changes were seen thereafter. In females, a decreasing trend was seen throughout the lifespan, with values reaching up to 76.0% of the initial peak value (p < 0.001). Similar to other skeletal sites, the alveolar bone exhibits sex differences and undergoes a reduction in BMD via the normal aging process.

Hormone replacement therapy and periodontitis progression in postmenopausal women: A prospective cohort study.

This study aimed to investigate the responses of periodontal environment to hormone replacement therapy (HRT) in postmenopausal women with or without periodontitis. HRT is a common and effective strategy for controlling menopausal symptoms, while the changes of periodontal environment under it, particularly in postmenopausal women with periodontitis, remain unclear. As a prospective cohort study, a total of 97 postmenopausal women receiving HRT were screened, including 47 with and 50 without periodontitis. Correspondingly, 97 women did not receiving HRT were screened as controls during the same period. The full-mouth sulcus bleeding index (SBI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured using periodontal probes. The levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the gingival crevicular fluid were measured using enzyme-linked immunosorbent assay. In addition, cone beam computed tomography was performed to measure the alveolar bone height (ABH) and bone mineral density (BMD). In postmenopausal women without periodontitis, no significantly changes on periodontal parameters were observed after HRT. In women with stage II periodontitis, SBI, BOP, IL-6, and TNF-α were significant decreased after one year and two years of HRT. Compared to the controls, women with stage II periodontitis who underwent HRT had significantly lower CAL and ABH and higher BMD in the second year. The incidence of at least one site with CAL increase ≥1 mm between baseline and 2 years was significantly lower in the HRT group than in the control group in women with stage II periodontitis. In addition, HRT was significantly associated with a decrease in SBI, BOP, IL-6, and TNF-α in the first year and with a decrease in CAL, SBI, BOP, IL-6, and ABH and an increase in BMD in the second year. In postmenopausal women with stage II periodontitis, HRT is associated with the alleviation of inflammation within two years and the remission of alveolar bone loss in the second year. HRT appears to decrease the incidence of CAL increase ≥1 mm within 2 years in women with periodontitis by inhibiting inflammation and alveolar bone loss.

Elevated alveolar bone mineral density in female patients undergoing bisphosphonate therapy: A pilot cross‐sectional study using intraoral radiographs

Elevated alveolar bone mineral density in female patients undergoing bisphosphonate therapy: A pilot cross‐sectional study using intraoral radiographs

Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia

Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg−1 of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3–7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.

Features of orthodontic treatment in patients with generalized periodontitis

The need for orthodontic treatment in patients with generalized periodontitis is unquestionable today. However, in the case of orthodontic treatment of patients with generalized periodontitis, it should be remembered that the orthodontic treatment itself can damage the periodontal tissues. Periodontologists should take this into account when choosing a method of orthodontic treatment. Considering these circumstances, the preparation "Calcinovа" was used to strengthen the bone mineralization of the alveolar process.Aim. To determine the effectiveness of orthodontic treatment of patients with generalized periodontitis using a drug to stimulate alveolar bone mineralization.Material and methods. This study was conducted on a group of 36 patients with generalized periodontitis of a young age (18-35 years) with the absence of autonomic dysfunction - a state of eutonia. Patients underwent orthodontic treatment. To strengthen the processes of bone mineralization of the alveolar bone, the patients of the main subgroup were prescribed the drug "Calcinova". All patients underwent a comprehensive examination of the periodontium with the determination of the necessary hygienic indices to assess the state of the periodontium during treatment.Results. The examination of patients with generalized periodontitis after carrying out appropriate measures of therapeutic treatment showed a significant improvement in the condition of periodontal tissues. The beneficial effect of orthodontic treatment and stimulation of alveolar bone mineralization on the periodontal condition of patients is shown. Particular dynamics of the pathological process under the influence of complex treatment have been established. Analysis of the obtained results confirms the need for orthodontic treatment of patients with generalized periodontitis using methods of bone mineralization stimulation. It is shown that their use increases the effectiveness of treatment of generalized periodontitis.Conclusions. The combination of orthodontic treatment and a drug that increases bone mineralization of the alveolar process significantly improves the periodontal condition of patients with generalized periodontitis. The effectiveness of the use of the drug "Calcinova" for stimulating bone mineralization of the alveolar process of patients and maintaining the level of attachment is shown.

Contributions of increased osteopontin and hypophosphatemia to dentoalveolar defects in osteomalacic Hyp mice.

X-linked hypophosphatemia (XLH) is an inherited disorder caused by inactivating mutations in the PHEX gene leading to renal phosphate wasting, rickets and osteomalacia. XLH is also associated with dentoalveolar mineralization defects in tooth enamel, dentin and cementum, and in alveolar bone, which lead to an increased prevalence of dental abscesses, periodontal disease and tooth loss. Genetic mouse experiments, and deficiencies in XLH patient therapies where treatments do not fully ameliorate mineralization defects, suggest that other pathogenic mechanisms may exist in XLH. The mineralization-inhibiting, secreted extracellular matrix phosphoprotein osteopontin (OPN, gene Spp1) is a substrate for the PHEX enzyme whereby extensive and inactivating degradation of inhibitory OPN by PHEX facilitates mineralization. Conversely, excess OPN accumulation in skeletal and dental tissues - for example in XLH where inactivating mutations in the PHEX gene limit degradation of inhibitory OPN, or as occurs in Fgf23-null mice - contributes to mineralization defects. We hypothesized that Spp1/OPN ablation in Hyp mice (a mouse model for XLH) would reduce dentoalveolar mineralization defects. Immunostaining revealed increased OPN in Hyp vs. wild-type (WT) alveolar bone, particularly in osteocyte lacunocanalicular networks where Hyp mice have characteristic hypomineralized peri-osteocytic lesions (POLs). Micro-computed tomography and histology showed that ablation of Spp1 in Hyp mice (Hyp;Spp1-/-) on a normal diet did not ameliorate bulk defects in enamel, dentin, or alveolar bone. On a high-phosphate diet, both Hyp and Hyp;Spp1-/- mice showed improved mineralization of enamel, dentin, and alveolar bone. Silver staining indicated Spp1 ablation did not improve alveolar or mandibular bone osteocyte POLs in Hyp mice; however, they were normalized by a high-phosphate diet in both Hyp and Hyp;Spp1-/- mice, although inducing increased OPN. Collectively, these data indicate that despite changes in OPN content in the dentoalveolar mineralized tissues, there exist other compensatory mineralization mechanisms that arise from knockout of Spp1/OPN in the Hyp background.

Micro-computed tomography evaluation of the effects of orthodontic force on immature maxillary first molars and alveolar bone mineral density of Sprague–Dawley rats

To investigate changes in the immature teeth of Sprague-Dawley rats during orthodontic treatment and to explore the changes in the peri-radicular alveolar bone through micro-computed tomography (CT). Twenty-five 26-day-old male Sprague-Dawley rats were included. The maxillary left first molar was moved mesially under a continuous force of 30 cN, and the right first molar served as the control. After orthodontic treatment for 7, 14, 21, 28, and 42 days, the root length, tooth volume, and alveolar bone mineral density (BMD) around the mesial root were measured through micro-CT. The immature teeth continued to elongate after application of orthodontic force. The root length on the force side was significantly smaller than that on the control side, whereas the differences in the volume change between both sides were not statistically significant. Alveolar bone in the coronal part of the compression and tension sides showed no difference in BMD between the experimental and control groups. The BMD of the experimental group decreased from day 14 to day 42 in the apical part of the compression side and increased from day 7 to day 42 in the apical part of the tension side. The BMD of the experimental group decreased in the root apex part on day 7. The root length and volume of immature teeth showed continued development under orthodontic forces. Alveolar bone resorption was observed on the compression side, and bone formation was observed on the tension side.

Comparison of the effects of two extraction methods on the alveolar ridge preservation of Maxillary Anterior Teeth.

To compare the effects of high-speed turbodrill root extraction and piezosurgery tooth socket enlargement on the alveolar ridge preservation of maxillary anterior teeth. Thirty-six clinically eligible patients admitted to the No.2 Hospital of Baoding or the Baoding First Central Hospital from January 2018 to November 2019 were selected and randomly divided into two groups. Group-A were extracted by high-speed turbodrill root extraction, while Group-B were extracted by piezosurgery tooth socket enlargement. After extraction, GBR bone grafting and soft tissue transplantation were performed on the extraction sockets. The extraction time, integrity rate of labial bone plate of the extraction socket, pain-free rate, satisfaction rate, reduction of the height and width of the alveolar ridge, alveolar bone mineral density score, and new bone contour score of the alveolar bone of two groups were compared. Group-B was significantly superior to Group-A in terms of tooth extraction time, pain-free rate, satisfaction rate and reduction of alveolar ridge height at three sites on the palatal side, with a statistically significant difference (p<0.05). Piezosurgery tooth socket enlargement is more worthy of clinical application due to its advantages of less impact on the preservation of the palatal alveolar ridge height of the maxillary anterior teeth, shorter tooth extraction time, postoperative pain-free rate and high final satisfaction rate.

The Bone Sialoprotein RGD Domain Modulates and Maintains Periodontal Development

Bone sialoprotein (gene: Ibsp; protein: BSP) is a multifunctional extracellular matrix protein present in bone, cementum, and dentin. Accumulating evidence supports BSP as a key regulator of mineralized tissue formation via evolutionarily conserved functional domains, including a C-terminal integrin-binding Arg-Gly-Asp (RGD) domain implicated in extracellular matrix–cell signaling. Ablation of Ibsp in mice (Ibsp−/−) results in impaired bone growth and mineralization and defective osteoclastogenesis, with effects in the craniofacial region including reduced acellular cementum formation, detachment of the periodontal ligament (PDL), alveolar bone hypomineralization, and severe periodontal breakdown. We hypothesized that BSP-RGD plays an important role in cementum and alveolar bone formation and mineralization, as well as periodontal function. This hypothesis was tested by replacing the RGD motif with a nonfunctional Lys-Ala-Glu (KAE) sequence in (IbspKAE/KAE) mice and OCCM.30 murine (IbspKAE) cementoblasts. The RGD domain was not critical for acellular or cellular cementum formation in IbspKAE/KAE mice. However, PDL volume and thickness were increased, and significantly more tartrate-resistant acid phosphatase–positive osteoclasts were found on alveolar bone surfaces of IbspKAE/KAE mice versus wild type mice. PDL organization was disrupted as indicated by picrosirius red stain, second harmonic generation imaging, dynamic mechanical analysis, and decreased asporin proteoglycan localization. In vitro studies implicated RGD functions in cell migration, adhesion, and mineralization, and this was confirmed by an ossicle implant model where cells lacking BSP-RGD showed substantial defects as compared with controls. In total, the BSP-RGD domain is implicated in periodontal development, though the scale and scope of changes indicated by in vitro studies indicate that other factors may partially compensate for and reduce the phenotypic severity of mice lacking BSP-RGD in vivo.

Between a rock and a hard place: Regulation of mineralization in the periodontium.

The periodontium supports and attaches teeth via mineralized and nonmineralized tissues. It consists of two, unique mineralized tissues, cementum and alveolar bone. In between these tissues, lies an unmineralized, fibrous periodontal ligament (PDL), which distributes occlusal forces, nourishes and invests teeth, and harbors progenitor cells for dentoalveolar repair. Many unanswered questions remain regarding periodontal biology. This review will focus on recent research providing insights into one enduring mystery: the precise regulation of the hard-soft tissue borders in the periodontium which define the interfaces of the cementum-PDL-alveolar bone structure. We will focus on advances in understanding the molecular mechanisms that maintain the unmineralized PDL "between a rock and a hard place" by regulating the mineralization of cementum and alveolar bone.

Influence of dental implantation on bone mineral density distribution: a pilot study.

PURPOSEMasticatory loading triggers active bone remodeling, altering alveolar bone mineral density (BMD). While dental implants are placed to bear masticatory loading, their influence on changing bone properties has not been fully investigated. Objective of this pilot study was to examine whether the dental implantation has an effect on BMD distribution of bone by comparing dentate, edentulous, and edentulous patients with implants.MATERIALS AND METHODSCone beam computed tomography (CBCT) images of 19 partially edentulous patients (Dent), 19 edentulous patients (Edent), and 16 edentulous patients who received implants in the mandible (Edent+Im), were obtained. CBCT images were also obtained from 5 patients within Edent+Im group, before implant placement and after implant loading. Basal cortical bone region of the mandible was digitally isolated. A histogram of gray levels proportional to BMD was obtained to assess mean, histogram standard deviation (HSD), fifth percentile of low and high values (Low5 and High5) of the BMD distribution. Multivariate analysis of variance and paired t-test were used to compare the BMD parameters among the 3 dental status groups and between pre- and post-implantation, respectively.RESULTSEdentulous patients with implants had significantly greater HSD and High5 values compared to edentulous patients (P < .013). All other comparisons were not significant (P > .097). Mean, HSD, and High5 values significantly increased after receiving implants (P < .022).CONCLUSIONThe current findings suggested that receiving dental implants promoted oral bone mineralization for edentulous patients. The longitudinal investigation could provide valuable information on understanding the effects of implantation on the behavior of oral bone quality.

Observation on the Effect of Bone Grafting Alone and Guided Tissue Regeneration Combined with Bone Grafting to Repair Periodontal Intraosseous Defects.

Objective To investigate the curative effect of guided tissue regeneration (GTR) combined with bone grafting and improve the aesthetic appearance of patients' gingiva. Methods A total of 86 patients with periodontal intraosseous defects were selected from February 2019 to February 2021. All the patients were divided into a control group and an observation group according to the random number table, with 43 patients in each group. Bone grafting was performed in the control group, while GTR was additionally used in the observation group on the basis of the control group. The surgical data and follow-up data were collected and organized. The alveolar bone mineral density, the change in the height of the bone defect, plaque index (PLI), sulcus hemorrhage index (SBI), PD, gingival recession (GR), clinical attachment loss (CAL), and other relevant data of the two groups in 6 months before and after surgery were compared. Six months after surgery, the cosmetic morphology of the patient's gums in the soft tissues around her teeth was evaluated. Results Six months after surgery, the alveolar bone density of patients in two groups increased compared with that before surgery, and the height of the bone defect decreased compared with that before surgery. The alveolar bone density of the observation group was higher than that of the control group, and the height of the bone defect was lower than that of the control group (P < 0.05). Six months after surgery, the PLI, SBI, PD, and CAL of patients in both groups were lower than those before surgery, while the GR was higher than that before surgery. PD and CAL values in the observation group were lower than those in the control group, and GR was higher than that in the control group (P < 0.05). Six months after surgery, there was no significant difference in PLI and SBI scores between the two groups (P < 0.05). Six months after surgery, the gingival cosmetic scores of the two groups of patients were higher than those before surgery. The observation group was higher than the control group (P < 0.05). Conclusion GTR combined with bone grafting has a good effect in the repair of periodontal intraosseous defects and can effectively promote the reconstruction and recovery of periodontal intraosseous defects in patients. At the same time, it can significantly improve the aesthetic appearance of patients' gums, with good clinical application value.

A Novel Modified-Curcumin Promotes Resolvin-Like Activity and Reduces Bone Loss in Diabetes-Induced Experimental Periodontitis.

PurposeClinically, it is challenging to manage diabetic patients with periodontitis. Biochemically, both involve a wide range of inflammatory/collagenolytic conditions which exacerbate each other in a “bi-directional manner.” However, standard treatments for this type of periodontitis rely on reducing the bacterial burden and less on controlling hyper-inflammation/excessive-collagenolysis. Thus, there is a crucial need for new therapeutic strategies to modulate this excessive host response and to promote enhanced resolution of inflammation. The aim of the current study is to evaluate the impact of a novel chemically-modified curcumin 2.24 (CMC2.24) on host inflammatory response in diabetic rats.MethodsType I diabetes was induced by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC2.24, or the vehicle-alone, was administered by oral gavage daily for 3 weeks to the diabetics. Micro-CT was used to analyze morphometric changes and quantify bone loss. MMPs were analyzed by gelatin zymography. Cell function was examined by cell migration assay, and cytokines and resolvins were measured by ELISA.ResultsIn this severe inflammatory disease model, administration of the pleiotropic CMC2.24 was found to normalize the excessive accumulation and impaired chemotactic activity of macrophages in peritoneal exudates, significantly decrease MMP-9 and pro-inflammatory cytokines to near normal levels, and markedly increase resolvin D1 (RvD1) levels in the thioglycolate-elicited peritoneal exudates (tPE). Similar effects on MMPs and RvD1 were observed in the non-elicited resident peritoneal washes (rPW). Regarding clinical relevance, CMC2.24 significantly inhibited the loss of alveolar bone height, volume and mineral density (ie, diabetes-induced periodontitis and osteoporosis).ConclusionIn conclusion, treating hyperglycemic diabetic rats with CMC2.24 (a tri-ketonic phenylaminocarbonyl curcumin) promotes the resolution of local and systemic inflammation, reduces bone loss, in addition to suppressing collagenolytic MMPs and pro-inflammatory cytokines, suggesting a novel therapeutic strategy for treating periodontitis complicated by other chronic diseases.

TGF-Beta Receptor II Is Critical for Osteogenic Progenitor Cell Proliferation and Differentiation During Postnatal Alveolar Bone Formation.

Transforming growth factor beta (TGFβ) signaling plays an important role during osteogenesis. However, most research in this area focuses on cortical and trabecular bone, whereas alveolar bone is largely overlooked. To address the role of TGFβR2 (the key receptor for TGFβ signaling) during postnatal alveolar bone development, we conditionally deleted Tgfβr2 in early mesenchymal progenitors by crossing Gli1-CreERT2; Tgfβr2flox/flox; R26RtdTomato mice (named early cKO) or in osteoblasts by crossing 3.2kb Col1-CreERT2; Tgfβr2 flox/flox; R26RtdTomato mice (named late cKO). Both cKO lines were induced at postnatal day 5 (P5) and mice were harvested at P28. Compared to the control littermates, early cKO mice exhibited significant reduction in alveolar bone mass and bone mineral density, with drastic defects in the periodontal ligament (PDL); conversely, the late cKO mice displayed very minor changes in alveolar bone. Mechanism studies showed a significant reduction in PCNA+ PDL cell numbers and OSX+ alveolar bone cell numbers, as well as disorganized PDL fibers with a great reduction in periostin (the most abundant extracellular matrix protein) on both mRNA and protein levels. We also showed a drastic reduction in β-catenin in the early cKO PDL and a great increase in SOST (a potent inhibitor of Wnt signaling). Based on these findings, we conclude that TGFβ signaling plays critical roles during early alveolar bone formation via the promotion of PDL mesenchymal progenitor proliferation and differentiation mechanisms.

Fibroblast Growth Factor 2 High Molecular Weight Isoforms in Dentoalveolar Mineralization.

Transgenic mice overexpressing human high molecular weight fibroblast growth factor 2 (HMWFGF2) isoforms in osteoblast and odontoblast lineages (HMWTg) exhibit decreased dentin and alveolar bone mineralization, enlarged pulp chamber, and increased fibroblast growth factor 23 (FGF23). We examined if the alveolar bone and dentin mineralization defects in HMWTg mice resulted from increased FGF23 expression and whether an FGF23 neutralizing antibody could rescue the hypomineralization phenotype. HMWTg and VectorTg control mice were given subcutaneous injections of FGF23 neutralizing antibody twice/week starting at postnatal day 21 for 6weeks. Since Calcitriol (1,25D) have direct effects in promoting bone mineralization, we also determined if 1,25D protects against the defective dentin and alveolar bone mineralization. Therefore, HMWTg mice were given subcutaneous injections of 1,25D daily or concomitantly with FGF23 neutralizing antibody for 6weeks. Our results showed that HMWTg mice displayed thickened predentin, alveolar bone hypomineralization, and enlarged pulp chambers. FGF23 neutralizing antibody and 1,25D monotherapy partially rescued the dentin mineralization defects and the enlarged pulp chamber phenotype in HMWTg mice. 1,25D alone was not sufficient to rescue the alveolar bone hypomineralization. Interestingly, HMWTg mice treated with both FGF23 neutralizing antibody and 1.25D further rescued the enlarged pulp chamber size, and dentin and alveolar bone mineralization defects. We conclude that the dentin and alveolar bone mineralization defects in HMWTg mice might result from increased FGF23 expression. Our results show a novel role of HMWFGF2 on dentoalveolar mineralization.