Improved Spatial Resolution Achieved by Chromatic Intensity Interferometry.

Interferometers are widely used in imaging technologies to achieve enhanced spatial resolution, but require that the incoming photons be indistinguishable. In previous work, we built and analyzed color erasure detectors, which expand the scope of intensity interferometry to accommodate sources of different colors. Here we demonstrate experimentally how color erasure detectors can achieve improved spatial resolution in an imaging task, well beyond the diffraction limit. Utilizing two 10.9-mm-aperture telescopes and a 0.8 m baseline, we measure the distance between a 1063.6 and a 1064.4 nm source separated by 4.2 mm at a distance of 1.43 km, which surpasses the diffraction limit of a single telescope by about 40 times. Moreover, chromatic intensity interferometry allows us to recover the phase of the Fourier transform of the imaged objects-a quantity that is, in the presence of modest noise, inaccessible to conventional intensity interferometry.

Chromatic interferometry with small frequency differences.

By developing a 'two-crystal' method for color erasure, we can broaden the scope of chromatic interferometry to include optical photons whose frequency difference falls outside of the 400 nm to 4500 nm wavelength range, which is the passband of a PPLN crystal. We demonstrate this possibility experimentally, by observing interference patterns between sources at 1064.4 nm and 1063.6 nm, corresponding to a frequency difference of about 200 GHz.

SOST, an LNGFR target, inhibits the osteogenic differentiation of rat ectomesenchymal stem cells.

OBJECTIVES: The aim of this study was to investigate whether sclerostin (SOST) regulates the osteogenic differentiation of rat ectomesenchymal stem cells (EMSCs) and whether SOST and low-affinity nerve growth factor receptor (LNGFR) regulate the osteogenic differentiation of EMSCs. MATERIALS AND METHODS: EMSCs were isolated from embryonic facial processes from an embryonic 12.5-day (E12.5d) pregnant Sprague-Dawley rat. LNGFR+ EMSCs and LNGFR- EMSCs were obtained by fluorescence-activated cell sorting and were subsequently induced to undergo osteogenic differentiation in vitro. SOST/LNGFR small-interfering RNAs and SOST/LNGFR overexpression plasmids were used to transfect EMSCs. RESULTS: LNGFR+ EMSCs displayed a higher osteogenic capacity and lower SOST levels compared with LNGFR- EMSCs. SOST silencing enhanced the osteogenic differentiation of LNGFR- EMSCs, while SOST overexpression attenuated the osteogenic differentiation of LNGFR+ EMSCs. Moreover, LNGFR was present upstream of SOST and strengthened the osteogenic differentiation of EMSCs by decreasing SOST. CONCLUSIONS: SOST alleviated the osteogenic differentiation of EMSCs, and LNGFR enhanced the osteogenic differentiation of EMSCs by decreasing SOST, suggesting that the LNGFR/SOST pathway may be a novel target for promoting dental tissue regeneration and engineering.

LNGFR targets the Wnt/ß-catenin pathway and promotes the osteogenic differentiation in rat ectomesenchymal stem cells.

Considerable evidence has shown that the Wnt/ß-catenin pathway is involved in osteogenic differentiation in various stem cells. However, the role of Wnt/ß-catenin pathway in regulating the osteogenic differentiation of rat ectomesenchymal stem cells (EMSCs), which are considered to be the progenitors of dental mesenchymal stem cells, remains unknown. In this study, we demonstrated that nuclear ß-catenin was upregulated during EMSC osteogenic differentiation. The Wnt signalling inhibitor IWR-1-endo inhibited EMSC osteogenic differentiation, while the Wnt signalling agonist SKL2001 promoted it. Moreover, nuclear ß-catenin was further upregulated by the overexpression of low-affinity nerve growth factor receptor (LNGFR) during EMSC osteogenic differentiation. Further experiments demonstrated that LNGFR overexpression enhanced EMSC osteogenic differentiation, while LNGFR silencing decreased it. Additionally, IWR-1-endo attenuated LNGFR-enhanced EMSC osteogenic differentiation. Collectively, our data reveal that LNGFR targets the Wnt/ß-catenin pathway and positively regulates EMSC osteogenic differentiation, suggesting that Wnt/ß-catenin pathway may be involved in the development of teeth and that the targeting Wnt/ß-catenin pathway may have great potential for applications in dental tissue engineering regeneration.

The root canal morphology in mandibular first premolars: a comparative evaluation of cone-beam computed tomography and micro-computed tomography.

OBJECTIVES: This study evaluated the accuracy of cone-beam computed tomography (CBCT) in detecting the root canal morphology of mandibular first premolars using micro-computed tomography (micro-CT) as a reference standard. MATERIALS AND METHODS: In total, 143 extracted human mandibular first premolars were selected and scanned using micro-CT and CBCT. The acquired images were used to evaluate the root canal morphology in each tooth, and evaluations were repeated after 2 weeks. The root canal configurations observed on the three-dimensional images were recorded, and the findings from both modalities were compared using chi-square tests. The actual agreement between the two modalities was assessed using kappa statistics. RESULTS: In total, the root morphologies in 136 mandibular first premolars were consistently identified by both CBCT and micro-CT: type I in 104, type III in five, type V in 20, and type IX in seven. Of the remaining seven teeth, the morphology in two, one, and four teeth was identified as type I, type VII, and type IX (type 1-3 in two and type 1-2-3 in two), respectively, by micro-CT and misdiagnosed as type III, type V, and type V, respectively, by CBCT. There were no significant differences between the two modalities with regard to the accurate detection of root canal configurations, with a kappa value of 0.886 for the actual agreement. CONCLUSIONS: Although CBCT may be accurate in detecting the root canal configuration in mandibular first premolars, it produces poorer image details compared with micro-CT. CLINICAL RELEVANCE: CBCT is a reliable radiological technique, but its accuracy in detecting details of the root canal morphology in mandibular first premolars, especially in some complex root canal configurations, needs to be improved.

Comparison of P75 NTR-positive and -negative etcomesenchymal stem cell odontogenic differentiation through epithelial-mesenchymal interaction.

OBJECTIVES: The aim of this study was to investigate differences of odonto-differentiation between P75 -neurotrophin receptor (P75 -NTR)-positive ectomesenchymal stem cells (P75+EMSCs) and P75 -NTR-negative ectomesenchymal stem cells (P75-EMSCs), and their underlying mechanisms. MATERIALS AND METHODS: Primary cranial neural crest-derived cells (CNC) were isolated from the first branchial arches, and P75+EMSCs and P75-EMSCs were sorted by fluorescence-activated cell sorting. Differentiation of P75+EMSCs or P75-EMSCs into odontoblast-like cells was induced by dental epithelial cells in vitro or in vivo. Differential gene expression profiles between P75+EMSCs and P75-EMSCs were analysed by microarray assay. Smad4-specific small interfering RNA and activator kartogenin were used to treat the cells, to evaluate effects of Smad4 in odonto-differentiation of P75+EMSCs or P75-EMSCs. RESULTS: Under induction of dental epithelium conditioned medium, P75+EMSCs had more mineralized node formation and higher expression of Dmp1 and Dspp compared to P75-EMSCs. In our in vivo study, graft of P75+EMSCs recombination with dental epithelium showed higher expression of DMP1 and DSP. Knock-down of Smad4 in P75+EMSCs significantly downregulated expression of DMP1 and DSP, while activation of Smad4 in P75-EMSCs by the activator kartogenin, significantly increased DSP and DMP1 expression. CONCLUSIONS: P75+EMSCs showed more odonto-differentiation potential than P75-EMSCs both in vivo and in vitro. Smad4 played a critical role in determination of odonto-differentiation potential of CNC-derived EMSCs.

DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis.

Multiple studies have shown that diabetes mellitus is an established risk factor for periodontitis. Recently mesenchymal stem cells derived from periodontal ligament (PDLSCs) have been utilized to reconstruct tissues destroyed by chronic inflammation. However, impact of periodontitis with diabetes mellitus on PDLSCs and mechanisms mediating effects of complex microenvironments remain poorly understood. In this study, we found multiple differentiation potential of PDLSCs from chronic periodontitis with diabetes mellitus donors (D-PDLSCs) was damaged significantly. Inhibition of NF-κB signaling could rescue osteogenic potential of PDLSCs from simple chronic periodontitis patients (P-PDLSCs), whereas did not promote D-PDLSCs osteogenesis. In addition, we found expression of DKK1 in D-PDLSCs did not respond to osteogenic signal and decreased osteogenic potential of D-PDLSCs treated with DKK1 could be reversed. To further elucidate different character between P-PDLSCs and D-PDLSCs, we treated PDLSCs with TNF-α and advanced glycation end products (AGEs), and find out AGEs which enhance effect of TNF-α in PDLSCs might mediate special personality of D-PDLSCs. The adverse effect of AGEs in PDLSCs could be reversed when PDLSCs were treated with DKK1. These results suggested DKK1 mediating WNT signaling might be a therapy target to rescue potential of PDLSCs in periodontitis with diabetes mellitus.

In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75(+) stem cells with dental follicle cell conditioned medium.

Cranial neural crest-derived cells (CNCCs) play important role in epithelial-mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75(+)) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75(+) CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75(+) cells, suggesting their differentiation along cementoblast-like lineage. p75(+) stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial-mesenchymal interactions in tooth morphogenesis.

Inhibited Wnt signaling causes age-dependent abnormalities in the bone matrix mineralization in the Apert syndrome FGFR2(S252W/+) mice.

Apert syndrome (AS) is a type of autosomal dominant disease characterized by premature fusion of the cranial sutures, severe syndactyly, and other abnormalities in internal organs. Approximately 70% of AS cases are caused by a single mutation, S252W, in fibroblast growth factor receptor 2 (FGFR2). Two groups have generated FGFR2 knock-in mice Fgfr2S252W/+ that exhibit features of AS. During the present study of AS using the Fgfr2S252W/+ mouse model, an age-related phenotype of bone homeostasis was discovered. The long bone mass was lower in 2 month old mutant mice than in age-matched controls but higher in 5 month old mutant mice. This unusual phenotype suggested that bone marrow-derived mesenchymal stem cells (BMSCs), which are vital to maintain bone homeostasis, might be involved. BMSCs were isolated from Fgfr2S252W/+ mice and found that S252W mutation could impair osteogenic differentiation BMSCs but enhance mineralization of more mature osteoblasts. A microarray analysis revealed that Wnt pathway inhibitors SRFP1/2/4 were up-regulated in mutant BMSCs. This work provides evidence to show that the Wnt/ß-catenin pathway is inhibited in both mutant BMSCs and osteoblasts, and differentiation defects of these cells can be ameliorated by Wnt3a treatment. The present study suggested that the bone abnormalities caused by deregulation of Wnt pathway may underlie the symptoms of AS.

A micro-computed tomography study of the relationship between radicular grooves and root canal morphology in mandibular first premolars.

OBJECTIVES: This study aims to explore the correlation between radicular grooves and root canal types by quantitatively detecting the radicular groove of mandibular first premolars using micro-computed tomography. MATERIALS AND METHODS: A total of 127 mandibular first premolars were scanned by micro-computed tomography, and 52 teeth with radicular grooves were identified. Details of root canal type and groove length, depth, and location were analyzed from three-dimensional images. RESULTS: A total of 40.9 % (52/127) of teeth had radicular grooves. Most of the grooves (69.5 %) were located on the mesial surface of the root. The prevalence of radicular grooves in single canals (17.4 %; 15/86) was lower than that in multiple and complex canals (90.2 %; 37/41); this difference was statistically significant (P < 0.001). The mean length and depth of radicular groove in type V (7.7 ± 2.16 and 0.87 ± 0.39 mm, respectively) and other types of canals (6.91 ± 2.67 and 0.63 ± 0.27 mm, respectively) were significantly longer and deeper than type I canals (6.06 ± 2.12 and 0.43 ± 0.14 mm, respectively). CONCLUSIONS: Multiple and complex canals had a higher incidence of radicular grooves and more complicated root morphology than single and simple canals. Therefore, the anatomy of radicular grooves may influence root canal morphology. CLINICAL RELEVANCE: The existence of a radicular groove is closely related to root anatomy and root canal morphology. Anatomical complexity increases the difficulty of root canal treatment and periodontal therapy; therefore, the current data may provide clinicians with a more thorough understanding of the relationship between radicular grooves and root canal morphology.

History of periodontitis as a risk factor for long-term survival of dental implants: a meta-analysis.

PURPOSE: The authors conducted a meta-analysis to determine the effect of a history of periodontitis on the long-term survival of dental implants. MATERIALS AND METHODS: An electronic search of PubMed and a supplemental manual search were conducted. Studies published in English through March 2013 were included in the meta-analysis. Survival rates, success rates, periodontal status, types of periodontitis, most recent follow-up time, and other information were extracted and analyzed. RESULTS: Thirteen studies involving 2,011 patients and 6,802 implants were included in the meta-analysis. The results revealed that a history of periodontitis, especially aggressive periodontitis, is associated with significantly higher risks of long-term implant failure versus a healthy periodontium (risk ratio [RR] = 1.03, 95% confidence interval [CI] = 1.02 to 1.04). Based on the limited number of included articles, a subgroup analysis showed that a history of periodontitis had no statistically significant effect on implant survival up to 100 months of follow-up (RR = 1.03, 95% CI = 0.99 to 1.06); however, it did significantly affect implant survival within a period of 101 to 200 months (RR = 1.03, 95% CI = 1.02 to 1.04). Some implant systems also significantly influenced the correlation between a history of periodontitis and implant survival. CONCLUSION: Within the limitations of this meta-analysis, a history of periodontitis is estimated to be a statistical risk factor for the long-term survival of dental implants. This negative effect would be most evident in patients with aggressive periodontitis, severe periodontitis, or after a longer follow-up.

Axonal regeneration and remyelination evaluation of chitosan/gelatin-based nerve guide combined with transforming growth factor-ß1 and Schwann cells.

Despite efforts in peripheral nerve injury and regeneration, it is difficult to achieve a functional recovery following extended peripheral nerve lesions. Even if artificial nerve conduit, cell components and growth factors can enhance nerve regeneration, integration in peripheral nerve repair and regeneration remains yet to be explored. For this study, we used chitosan/gelatin nerve graft constructed with collagenous matrices as a vehicle for Schwann cells and transforming growth factor-ß1 to bridge a 10-mm gap of the sciatic nerve and explored the feasibility of improving regeneration and reinnervation in rats. The nerve regeneration was assessed with functional recovery, electrophysiological test, retrograde labeling, and immunohistochemistry analysis during the post-operative period of 16 weeks. The results showed that the internal sides of the conduits were compact enough to prevent the connective tissues from ingrowth. Nerve conduction velocity, average regenerated myelin area, and myelinated axon count were similar to those treated with autograft (p > 0.05) but significantly higher than those bridged with chitosan/gelatin nerve graft alone (p < 0.05). Evidences from retrograde labeling and immunohistochemistry analysis are further provided in support of improving axonal regeneration and remyelination. A designed graft incorporating all of the tissue-engineering strategies for peripheral nerve regeneration may provide great progress in tissue engineering for nerve repair.

The Fgfr2(S252W/+) mutation in mice retards mandible formation and reduces bone mass as in human Apert syndrome.

Apert syndrome is a common craniosynostosis caused by gain-of-function missense mutations of fibroblast growth factor receptor 2 (FGFR2). Mice with the FGFR2 S252W mutation can elucidate the mechanism by which the human Apert syndrome phenotypes arise. However, many studies have focused on mutant skull and long bone malformation, only few studies have focused on mandible changes. Bone formation and micro-architecture between 28- and 56-day-old mutant mice and controls were compared to investigate the changes in the mandibular micro-architecture caused by the Fgfr2(S252W/+) mutation to provide a basis for exploring the pathogenesis and therapeutic measures of human Apert syndrome. Fgfr2(S252W/+) mutant mice were established, and their general characteristics, including weight, naso-anal length, and calcium and phosphate content in serum and bone were tested. Calcein labeling, tartrate-resistant acid phosphatase staining and toluidine blue staining were used to detect osteoblast and osteoclast activities. H&E staining and micro-CT detection were used to test micro-architecture changes. The changes in mineral apposition rate and micro-architecture of the Fgfr2(S252W/+) mice were statistically significant; however, the magnitude of the micro-architecture became less with age. The Fgfr2(S252W/+) mutation may retard mandibular bone formation, decreased bone volume, and compromised skeletal architecture by regulating both osteoblastogenesis and osteoclastogenesis.

A micro-computed tomography study of the root canal morphology of the mandibular first premolar in a population from southwestern China.

OBJECTIVES: This study aimed to investigate the root canal morphology of mandibular first premolar teeth in a population from southwestern China by micro-computed tomography (micro-CT). MATERIALS AND METHODS: Human mandibular first premolars (115) were selected and prepared for micro-CT analysis with a slice thickness of 30 µm. Details of root canal orifices, canals, accessory canals, apical foramina-apical delta intercanal communication, loops and isthmuses, and mesial invagination were analyzed from reconstructed three-dimensional (3D) images. RESULTS: Canal patterns categorized according to the classification defined by Vertucci (Endod Top 10:3-29, 2005) as types I (65.2%), III (2.6%), V (22.6%), and VII were identified (0.9%). Accessory canals were present in 35.7% of the samples and were predominantly located in the apical third of the root. A single apical foramen was observed in 50.4% of the samples and two or three foramina in 28.7% and 14.8%, respectively. Apical delta was identified in 6.1% of the samples and the prevalence of intercanal communication and loops was 3.5% and 7%, respectively. Mesial invagination of the root was identified in 27.8% of the samples, the majority of which contained multiple canals. CONCLUSIONS: The data obtained in this study revealed complex root morphology with high prevalence of multiple canals, more than half of which exhibited type I canal patterns. CLINICAL RELEVANCE: Micro-CT was used as a noninvasive technique for 3D investigation of root canal morphology in the mandibular first premolars of a population from southwestern China. Furthermore, data obtained revealed complex anatomy of various types.

Characterization of p75(+) ectomesenchymal stem cells from rat embryonic facial process tissue.

Several populations of stem cells, including those from the dental pulp and periodontal ligament, have been isolated from different parts of the tooth and periodontium. The characteristics of such stem cells have been reported as well. However, as a common progenitor of these cells, ectomesenchymal stem cells (EMSCs), derived from the cranial neural crest have yet to be fully characterized. The aim of this study was to better understand the characteristics of EMSCs isolated from rat embryonic facial processes. Immunohistochemical staining showed that EMSCs had migrated to rat facial processes at E11.5, while the absence of epithelial invagination or tooth-like epithelium suggested that any epithelial-mesenchymal interactions were limited at this stage. The p75 neurotrophin receptor (p75NTR), a typical neural crest marker, was used to select p75NTR-positive EMSCs (p75(+) EMSCs), which were found to show a homogeneous fibroblast-like morphology and little change in the growth curve, proliferation capacity, and cell phenotype during cell passage. They also displayed the capacity to differentiate into diverse cell types under chemically defined conditions in vitro. p75(+) EMSCs proved to be homogeneous, stable in vitro and potentially capable of multiple lineages, suggesting their potential for application in dental or orofacial tissue engineering.

[The observation of surface morphology of enamal and temperature of dental pulp cavity in vitro after irradiated by Er:YAG laser].

OBJECTIVE: To observe the changes of surface morphology and temperature of dental pulp cavity in vitro after irradiated by Er:YAG laser with different energy and irradiation time. METHODS: All of the 96 samples from 24 teeth in vitro were collected from dental clinical departments then divided into two groups (group A and group B) randomly. We chose the energy of 20 Hz, and 1, 2, 3, 4, 5, 6 W to treat the samples in group A and group B and the irradiation time was 10s or 20s. We recorded the temperature changes of dental pulp cavity by digital thermometer and observe the morphology of tooth enamel by scanning electron microscope (SEM). RESULTS: With the extension of irradiation time and increasing of energy, the temperatures of dental pulp cavity were significantly increased after the treatment of Er: YAG laser. The two groups of tooth enamel surface morphology were changed after irradiated by Er: YAG laser with different energy and irradiation time. However, there was no melting and carbonation on the surface of tooth enamel after the treatment of Er:YAG laser in two groups. CONCLUSION: The temperatures of dental pulp cavity were increased after irradiated by increasing laser energy density fom 1 W to 6 W. No melting or carbonized phenomenon was found in enamel within the energy of 1 W to 6 W. All the data would provide evidences for clinical treatment of cavity.

[Comparative study of root canal morphology of mandibular first premolar by micro-CT and radio visio graphy].

OBJECTIVE: To compare the consistency of root canal configuration types of mandibular first premolar by using micro-CT and radio visio graphy (RVG). METHODS: One hundred extracted mandibular first premolars with complete dental root and apex which received no endodontic treatment were randomly selected. Each tooth was radiographed with RVG through a buccolingual and mesiodistal direction, and then scanned with micro-CT and reconstructed. The classifications of the root canal types according to Vertucci's type with the two methods were compared. RESULTS: The canal patterns were classified as type I (67%), type III (3%), type V (18%), type VII (2%), additional type (10%) with micro-CT and canal patterns as type I (71%), type III (2%), type V (23%), type VII (1%), additional type (3%) with RVG. 63% of teeth showed one canal in both micro-CT and RVG. Only 25% of teeth were diagnosed as complex canal by the same canal type in both micro-CT and RVG. The Kappa value between micro-CT and RVG was 0.541 which suggested that the two kinds of methods had intermediate consistency. 82.8% of the premolars with root groove had two or more than two canals. CONCLUSION: Although RVG can basically reflect the root canal system type of the mandibular first premolars in vitro, it offers poor accuracy images to complex root canals. Micro-CT three-dimensional images could clearly and precisely display the root canal system morphology of the mandibular first pre-molars in vitro.

A micro-computed tomography study of the location and curvature of the lingual canal in the mandibular first premolar with two canals originating from a single canal.

INTRODUCTION: Little is known about the lingual canal in the Vertucci type V mandibular first premolar. This study investigated the location of the lingual canal orifice and the curvature of the lingual canal by using micro-computed tomography. METHODS: One hundred fifteen mandibular first premolars were scanned by micro-computed tomography, reconstructed 3-dimensionally by using Mimics 10.01 software, and displayed in parallel projection mode. Twenty-six teeth with Vertucci type V canal were selected for further study. The lingual canal orifice was located by measurements made in both lingual and proximal views. The angle alpha (α) between the start of the lingual canal and the main canal and the angle beta (ß) of the curvature of lingual canal were also measured. RESULTS: In proximal view, 69% of lingual canals were located in the middle third of the tooth and the remainder in the apical third. In lingual view, 73% were located in the middle third of the root and the remainder in the coronal third. Mean angle α and angle ß were 33.54° and 26.66°, respectively, in proximal view and 8.31° and 11.31°, respectively, in lingual view (P < .05). The highest values of angles α and ß were observed in proximal view (65.24°and 43.39°, respectively). In most cases, angles α and ß were severely curved in proximal view and straight or only slightly curved in lingual view. CONCLUSIONS: Detailed information on the lingual canal is essential for successful endodontic treatment in patients with mandibular first premolar. The view used for imaging influences the information obtained.

Effects of systemic ornidazole, systemic and local compound ornidazole and pefloxacin mesylate on experimental periodontitis in rats.

BACKGROUND: The purpose of the current study is to evaluate the effects of systemic ornidazole (SO) and systemic and local compound ornidazole and pefloxacin mesylate (SCOPM/LCOMP) on the inflammatory response associated with rat experimental chronic periodontitis (ECP) in sites with subgingival debridement. MATERIAL/METHODS: Periodontitis was induced in male Sprague-Dawley rats by placing a thin steel ligature around the upper first molars and inoculating them with Porphyromonas gingivalis 381. After the successful induction of the rat ECP, the periodontitis rats were randomly divided into 3 different combined treatment groups: (A) SO with scaling and root planing (SRP); (B) SCOMP with SRP; and (C) LCOMP with SRP. After 2 weeks the effects of the treatments were evaluated based on gingivitis, plaque index, probing pocket depth, aspartate aminotransferase, alveolar bone loss, and hematoxylin-eosin staining of the region around the first molars. RESULTS: After treatment, comparison with ECP was performed. The mean percentage reductions of SBI in SO, SCOPM, and LCOPM were 27.73%, 33.61%, and 58.82%, respectively. Those of PI were 33.20%, 42.80%, and 60.00%; those of PPD were 48.66%, 55.70%, and 72.48%; those of GCF-AST were 41.64%, 49.03%, and 66.42%; and those of ABL were 41.19%, 43.63%, and 54.47%, respectively. The inflammatory score of H&E showed median scores of 2.5, 1.75, 1.63, and 0.95 for ECP, SO, SCOMP, and LCOMP, respectively. All 3 treatment groups exhibited significantly reduced inflammation indicators (P<0.05). Of the 3, group C was the most effective (P<0.05). CONCLUSIONS: Although all the combined treatment groups responded to therapy with significant resolution of the infection, adjunctive LCOMP therapy is more effective for periodontitis.

High levels of ß-catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway.

Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self-renewal makes them an excellent cell source for bone regeneration and repair. However, their bone-regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of ß-catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P-PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of ß-catenin in P-PDLSCs than in H-PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of ß-catenin suppresses the noncanonical Wnt/Ca(2+) pathway, leading to increased proliferation but reduced osteogenic differentiation of P-PDLSCs. Downregulation of the levels of ß-catenin by treatment with dickkopf-1 (DKK-1) leads to activation of the noncanonical Wnt/Ca(2+) pathway, which, in turn, results in the promotion of osteogenic differentiation in P-PDLSCs. Interestingly, ß-catenin can affect both the canonical Wnt/ß-catenin pathway and the noncanonical Wnt/Ca(2+) pathway. Our data indicate that ß-catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments.