Deciduous pulp tissue implantation into the root canal of mandibular incisor resulted in pulp revascularization: a case report with a 5-year follow-up.

To explore a new method to implant deciduous tooth pulp into the canal of young permanent teeth with necrotic pulps and apical periodontitis for the regenerative endodontic treatment of tooth no: 41 in a 7-year-old male. Briefly, 1.5% Sodium Hypochlorite (NaOCl) irrigation and calcium hydroxide-iodoform paste were used as root canal disinfectant at the first visit. After 2 weeks, the intracanal medication was removed, and the root canal was slowly rinsed with 17% Ethylene Diamine Tetraacetic Acid (EDTA), followed by flushing with 20 mL saline and then drying with paper points. Tooth no: 72 was extracted, and its pulp was extracted and subsequently implanted into the disinfected root canal along with induced apical bleeding. Calcium hydroxide iodoform paste was gently placed over the bleeding clot, and after forming a mineral trioxide aggregate (MTA) coronal barrier, the accessed cavities were restored using Z350 resin composite. The root developments were evaluated via radiographic imaging at 6 months, 1 year and 5 years after treatment. Imaging and clinical analysis showed closure of the apical foramen, thickening of the root canal wall, and satisfactory root length growth. Autologous transplantation might be useful to regenerate dental pulp in necrotic young permanent teeth.

Assessment of knowledge, attitude, and practice on early childhood caries among dental undergraduates and residents in China.

BACKGROUND: Early childhood caries (ECC) causes severe, widespread oral health issues in children. Dental undergraduates and residents are expected to have a solid understanding of ECC for children's oral health promotion. This study aimed to evaluate the knowledge, attitude, and clinical practice on ECC among dental undergraduates and residents in China. METHODS: A 23-item electronic questionnaire was distributed to 598 dental undergraduates (4th- and 5th-year undergraduates) and residents (1st-, 2nd-, and 3rd-year residents) at the School of Stomatology, Wuhan University, China (in April-May 2023). SPSS Statistics was used to analyze the data using the Chi-square test at a significance level of 0.05. RESULTS: A total of 422 questionnaires were completed by participants (recovery rate: 70.6%) from various academic levels. Around 77.3% of participants had heard of ECC (mainly from textbooks), and only 27.5% considered themselves familiar with it. Residents (79.8%) had higher risk awareness of ECC on children's overall health than undergraduates (58.3%) (p < 0.05), but only 54.0% of participants correctly defined ECC. Most participants had a positive understanding of ECC's pathogenic factors and preventive measures, including feeding patterns (71.6%), fluoride application (93.4%), and teeth cleaning (93.1%). Furthermore, only 50.2% of participants encountered ECC cases in clinic. CONCLUSIONS: Despite having a suboptimal level of ECC-related knowledge and practice, dental undergraduates and residents in China demonstrated a more positive attitude towards its etiology-based prevention. Strengthening ECC education, guidance, and practice may enable them to gain a better understanding of ECC learning, which would benefit children's oral health.

Importance of serum IRAK3 as a biochemical marker in relation to severity and neurological outcome of human severe traumatic brain injury: A prospective longitudinal cohort study.

BACKGROUND: Interleukin-1 receptor-associated kinase 3 (IRAK3) may modulate inflammation in brain immunity. We determined the prognostic role of serum IRAK3 in severe traumatic brain injury (sTBI). METHODS: In this prospective longitudinal cohort study, serum IRAK3 concentrations of 131 sTBI patients and 131 controls were quantified. Extended Glasgow outcome scale (GOSE) scores of 1-4 at 180 days after trauma signified a poor prognosis. Univariate and multivariate analyses were sequentially adopted to appraise severity correlations and prognosis associations. RESULTS: There were significantly higher serum IRAK3 concentrations in patients than in controls. Serum IRAK3 concentrations of patients were independently correlated with Glasgow coma scale (GCS) scores, Rotterdam computed tomography (CT) scores and posttraumatic180-day GOSE scores. Also, IRAK3 concentrations were independently associated with 180-day poor prognosis, but not with death. Prognosis prediction model, in which GCS scores, Rotterdam scores and serum IRAK3 concentrations were merged, was portrayed using the nomogram. The model was rather stable, clinically usable and efficiently discriminative of poor prognosis under calibration curve, decision curve and receiver operating characteristic curve. CONCLUSIONS: A substantial enhancement of serum IRAK3 concentrations after head trauma is independently related to severity and neurological outcome, substantializing serum IRAK3 as a promising prognostic biomarker of sTBI.

Treatment outcomes of permanent teeth with uncomplicated and complicated crown fractures and factors associated with pulp survival: A retrospective study.

BACKGROUND: Crown fracture is the most common injury in permanent teeth. This study aimed to evaluate the treatment outcomes of permanent teeth with uncomplicated and complicated crown fractures and to investigate potential factors. MATERIALS AND METHODS: This retrospective study included patients who experienced crown fractures in permanent teeth from 2018 to 2021 with at least 12 months of follow-up. All complicated crown fractured teeth were treated with pulpotomy, while for teeth with uncomplicated crown fractures, three treatments (restoration, indirect pulp capping, or pulpotomy) were employed. The chi-square test was used to compare the prognosis of teeth with uncomplicated and complicated crown fractures. Potential factors associated with pulp survival including gender, interval, root development, enamel infraction, mobility, concomitant luxation injury, treatment, and coronal restoration were identified via Cox regression analysis. RESULTS: A total of 307 teeth from 220 children (average age = 9.3 ± 1.4 years; age range, 6-14 years) with a median follow-up of 23 months were included, and 82.1% of all teeth had immature roots. Complicated crown fractured teeth (93.6%, 102/109) had a significantly higher success rate compared with uncomplicated crown fractured teeth (85.4%, 169/198) (p < .05). Pulpotomy (96.9%) had the highest success rate of all treatments for uncomplicated crown fractures, followed by only restoration (85.0%) and indirect pulp capping (76.9%). The success rate of teeth that received pulpotomy was significantly higher than those treated by indirect pulp capping (p < .05). In uncomplicated crown fractures, teeth with Class II mobility were more vulnerable to failure than teeth without abnormal mobility (HR = 34.83; 95% CI, 9.59-126.56; p < .05); teeth that received pulpotomy were less prone to failure than teeth that received indirect pulp capping (HR = 13.53; 95% CI, 1.58-115.72; p < .05). CONCLUSION: Crown fractures treated with conservative pulp treatments had a relatively highly favorable prognosis. The prognosis of uncomplicated crown fractured teeth was impacted by the severity of periodontal injury and treatment strategies. Accurate diagnosis and identification of micro-exposures are important. Dentists should take multiple risk factors into account and select optimal treatment strategies.

Treatment outcomes of immature permanent necrotic evaginated teeth: A retrospective study comparing regenerative endodontic procedures with apexification.

BACKGROUND: Few studies have compared the outcomes of regenerative endodontic procedures (REPs) and calcium hydroxide apexification focusing on necrotic teeth with dens evaginatus. AIM: To qualitatively and quantitatively compare the treatment outcomes of REPs and calcium hydroxide apexification in teeth with dens evaginatus. DESIGN: Immature permanent necrotic evaginated teeth treated with REPs or calcium hydroxide apexification for a follow-up period of at least 12 months were included. Tooth success and survival rates were analyzed. Changes in radiographic root length, apical diameter, and radiographic root area (RRA) were quantified. Prognostic factors that might influence RRA were identified via multivariate linear regression analysis. RESULTS: A total of 112 teeth (50 REP cases and 62 apexification cases) with a median follow-up period of 26.5 months were included. Regenerative endodontic procedures and calcium hydroxide apexification exhibited similar satisfactory success and survival rates (p > .05). Additionally, 88 teeth were quantitatively analyzed. The REP group presented a significantly greater percentage increase in RRA and less decrease in apical diameter than the calcium hydroxide apexification group (p < .05). Teeth treated with REPs and with Stages 7 and 8 of root development showed a better gain in RRA (p < .05). CONCLUSION: While REP and calcium hydroxide apexification had similar success and survival rates, teeth with REPs showed an increase in RRA, indicating that REP is the preferred choice.

A novel DSPP frameshift mutation causing dentin dysplasia type 2 and disease management strategies.

The present study aims to investigate the mutation in a Chinese family with dentin dysplasia type II (DD-II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and cosegregation analysis within the enrolled family were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analyzed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants was performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was cosegregated in the family. The immature permanent teeth of patients with DD-II presented with X-shaped root canal phenotypes. Most of the identified mutations for DD-II were clustered in the DPP region between nucleotides 1686-2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD-II. The locus involving nucleotides 1686-2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD-II at different stages is important to avoid the development of secondary dental lesions.

Evaluation of concentrated growth factor and blood clot as scaffolds in regenerative endodontic procedures: A retrospective study.

The study aims to investigate and compare the success rate of concentrated growth factor (CGF) and blood clot (BC) as scaffolds in regenerative endodontic procedures (REPs). Immature permanent necrotic teeth treated by REPs with at least a 6-month follow-up were included. These teeth were divided into the CGF (53 teeth) and BC (68 teeth) groups. Treatment outcomes were assessed using a combined clinical and radiographic scoring system. The total success rate was 91.74% over a mean follow-up period of 23.15 months. There was no significant difference between the CGF group (86.79%) and BC group (95.59%). The success rate of traumatic teeth (84.31%) was significantly lower than that of teeth with developmental dental anomalies (98.39%) (p < 0.05). CGF may be a suitable alternative scaffold in REPs when adequate bleeding cannot be achieved. Moreover, compared to developmental dental anomalies, traumatic teeth treated by REPs may be more vulnerable to failure.

Mutation analysis in patients with nonsyndromic tooth agenesis using exome sequencing.

BACKGROUND: Tooth agenesis (TA) is a congenital abnormality that may present as syndromic or nonsyndromic. Considering its complex genetic aetiology, the aim of this study was to uncover the pathogenic mutants in patients with nonsyndromic TA and analyse the characteristics of these mutants. METHODS: Exome sequencing was performed to detect pathogenic variants in 72 patients from 43 unrelated families with nonsyndromic TA. All candidate variants were validated using Sanger sequencing. Bioinformatics and conformational analyses were performed to determine the pathogenic mechanisms of the mutants. RESULTS: The following eight mutations (six novel and two known) in six genes were identified in eight families: WNT10A [c.742C > T (p.R248*)], LRP6 [c.1518G > A (p.W506*), c.2791 + 1G > T], AXIN2 [c.133_134insGCCAGG (p.44_45insGQ)], PAX9 [c.439C > T (p.Q147*), c.453_454insCCAGC (p.L154QfsTer60)], MSX1 [c.603_604del (p.A203GfsTer10)] and PITX2 [c.522C > G (p.Y174*)]. Bioinformatics and conformational analyses showed that the protein structures were severely altered in these mutants, and indicated that these structural abnormalities may cause functional disabilities. CONCLUSIONS: Our study extends the mutation spectrum in patients with nonsyndromic TA and provides valuable data for genetic counselling. The pathogenic mechanisms of TA in patients/families with unknown causative variants need to be explored further.

Expert consensus on early childhood caries management.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.

Treatment Outcomes of Regenerative Endodontic Procedures in Traumatized Immature Permanent Necrotic Teeth: A Retrospective Study.

INTRODUCTION: This retrospective study aimed to evaluate the clinical and radiographic outcomes of regenerative endodontic procedures (REPs) for traumatic immature permanent teeth. Meanwhile, predictors influencing treatment outcomes were also analyzed to provide evidence for the management of immature teeth after different traumatic scenarios. METHODS: Traumatized immature permanent teeth diagnosed with pulp necrosis treated by REPs using blood clot or concentrated growth factor scaffolds with at least 6 months of follow-up were included from 2012 to 2021. Treatment outcomes were categorized as a success or failure and survival. Further root development was assessed in terms of the percentage changes in the apical diameter, root length, and radiographic root area. Among different injury types, the clinical and radiographic outcomes of REPs were evaluated by the Fisher exact test and the Kruskal-Wallis test, respectively. Survival analysis and Cox regression analysis were performed to identify significant predictors affecting outcomes. RESULTS: Sixty-two teeth with a mean of 22.3 months of follow-up satisfied the criteria, and 80.6% of the teeth had a successful outcome. A significant change was observed in a decrease of the apical diameter (69.3%) and an increase of the radiographic root area (22.6%) after REPs. Among different injury types, the success rates of REPs were as follows: fracture, 84.6%; luxation, 83.3%; combined injuries, 78.6%; and avulsion, 33.3% (P > .05). Fractured teeth had a significantly greater decrease of the apical diameter than combined injuries (P < .05). Avulsion was more prone to developing root resorption than fracture (P < .05). Scaffold was a significant predictor for success; a blood clot had a significantly reduced risk for failure than concentrated growth factor (hazard ratio = 16; 95% confidence interval, 2.1-125.2; P < .001). CONCLUSIONS: REPs provided satisfactory outcomes in traumatized immature permanent necrotic teeth. However, severe injuries, especially avulsion, should be determined carefully to perform REPs when resorption is expected. Scaffold selection may be an important consideration.

Changes in paediatric dental clinic after reopening during COVID-19 pandemic in Wuhan: a retrospective study.

OBJECTIVES: Affected by COVID-19 pandemic, The Department of Paediatric Dentistry of School and Hospital of Stomatology, Wuhan University was closed in late January 2020, and resumed on 20 April. Our study aimed to explore the effects of COVID-19 pandemic on paediatric dental services which might assist global paediatric dentists to build confidence and make appropriate policies under the pandemic. DESIGN: A retrospective study was performed. Medical records of patients were retrieved but without any private information, including patient name, ID number and address. PARTICIPANTS: All data of the patients from 20 April to 31 July in 2020 and 2019 were extracted and analysed including demographics, dental diagnosis and treatment methods. A total of 18 198 patients were included in the study. RESULTS: During this period, no medical staff or patient was infected with COVID-19 due to dental services. A total of 6485 in 2020 but 11 713 during the same period in 2019 visited the department. Compared with 2019, gender distribution did not change, but age distribution changed with an increase under 6-year-old. The diagnoses including caries, retained primary teeth, malocclusion, deep pits and fissures changed significantly, while pulpitis, apical periodontitis, tooth trauma, early loss of primary teeth, supernumerary teeth showed little change. Aerosol generating procedures were adopted less frequently overall in this period. CONCLUSIONS: The reopening of paediatric dental services is proceeding steadily with significant changes in the characteristics of the patients and treatment procedures.

Experts' consensus on space management of mixed dentition.

The mixed dentition stage is the period between primary and permanent dentition. The following biological processes are complicated and variable: jaw growth, development of inherited permanent teeth embryo, physiological absorption of primary teeth, restoration of surrounding alveolar bones, and growth and function establishment of soft tissues. For the normal development of the jaw, the establishment of the good occlusion relationship, development, and function of soft tissue is very important, whether or not the primary teeth are normally replaced by the permanent teeth in the mixed dentition stage. The eruption space is linked to the normal replacement of primary and permanent teeth. The presence of a mixed dentition space results in the incidence and progression of malocclusion and impacts the normal growth and development of the occlusion, jaw, and face. Space management in the mixed dentition stage is a crucial means to prevent and reduce malocclusion. The following were discussed and analyzed: the possible space problems, why the size of the space was affected, the content that needs to be assessed, and the methods of space management in the mixed dentition that can be used to unify and standardize the management of mixed dentition. This paper was developed to serve as a guide for regulated space management during the mixed dentition period.

The additional benefit of professional fluoride application for children as an adjunct to regular fluoride toothpaste: a systematic review and meta-analysis.

OBJECTIVE: To assess whether professional fluoride application (PFA) used in addition to regular fluoride toothpaste (RFT, ≥ 1,000 ppm) is more effective than RFT alone in children. MATERIALS AND METHODS: A systematic search was conducted using the PubMed, Embase, Google Scholar and CENTRAL databases. Randomized controlled trials (RCTs) comparing the effectiveness of RFT + PFA and RFT alone were included. Meta-analyses with random-effects models were performed. The certainty of evidence was assessed using the GRADE approach. RESULTS: A total of 2,729 records were identified from electronic and manual searches, which were screened by two reviewers independently and in duplicate. Six RCTs (5,034 participants) were included, of which four had high risk of bias and two had unclear risk of bias. The PFA used in all these trials was fluoride varnish (FV). In meta-analyses, no significant difference was observed between participants receiving FV + RFT and RFT alone of d(m/e)fs increment (mean difference (MD) - 0.17, 95% confidence interval (CI) - 0.60 to 0.26, P = 0.43, I2 = 38%; 6 trials, 5,034 participants, moderate certainty evidence), incidence of caries (risk ratio (RR) 0.91, 95% CI 0.80 to 1.05, P = 0.21, I2 = 41%; 4 trials, 4,487 participants, moderate certainty evidence) or changes in prevalence of caries (RR 0.89, 95% CI 0.78 to 1.01, P = 0.07, I2 = 0%, 4 trials, 4,189 participants, low certainty evidence). CONCLUSIONS: Low to moderate certainty evidence suggests that FV does not have significant additional caries-preventive benefit for children (under 8 years old) when provided as an adjunct to daily tooth brushing with RFT (≥ 1,000 ppm). There is insufficient evidence regarding the additional benefit of other PFA interventions. CLINICAL RELEVANCE: The decision to apply FV to children needs to be made in light of their actual usage of RFT. TRIAL REGISTRATION: PROSPERO (CRD42020165270).

Online consultation and emergency management in paediatric dentistry during the COVID-19 epidemic in Wuhan: A retrospective study.

BACKGROUND: The COVID-19 pandemic posed a great challenge to paediatric dentistry, which confronted with the restriction of service and resource shortage. AIM: To retrospectively analyse the information of children's dental online health consultation during the COVID-19 pandemic in China, and to provide methods to distinguish between dental emergencies and non-emergencies as well as their management. DESIGN: We collected all the online consultation information in Dept. of Paediatric dentistry, School & Hospital of Stomatology, Wuhan University, from 2 February to 31 March 2020, and extracted the information of age, gender, reason for consultation, description of symptom, and preliminary diagnosis of the children. RESULTS: A total of 474 online consultations of paediatric dentistry were included within 59 days during lockdown, and 190 (40.1%) were dental emergencies and 284 (59.9%) non-emergencies. Of 190 emergency consultations, 186 (97.9%) showed swelling, pain, and trauma with or without systemic symptoms. Among 284 non-emergency consultations, retained primary teeth (n = 126) and orthodontic consultation (n = 53) were the most common reasons for consultation. CONCLUSION: The paediatric emergency and non-emergency problems should be clearly distinguished and sufficient instructions provided in the special period of COVID-19. Priorities also should be set to deal with urgent conditions after the release of lockdown.

Is it necessary for children to receive professional fluoride in addition to regular fluoride toothpaste? Protocol for a systematic review.

INTRODUCTION: Regular toothbrushing with fluoride toothpaste is a fundamental intervention for caries prevention. Professional fluoride application (PFA) is widely considered a beneficial supplement to the routine use of fluoride toothpaste. However, some recent studies have failed to demonstrate the preventive effect of PFA. In addition, an increasing number of studies have highlighted the potential adverse effects of fluoride. However, little information exists on the effectiveness of additional PFA. The objective of this review is to systematically analyse the efficacy of PFA in addition to regular fluoride toothpaste among children under the age of 16. METHOD AND ANALYSIS: We will search the PubMed, Embase, Google Scholar and Cochrane Central Register of Controlled Trials databases for randomised controlled trials without language or publication date restrictions. Additional studies will be identified by manually searching the reference lists of the included studies and relevant reviews. At least two authors will carry out the selection of studies independently and in duplicate. The Cochrane Risk of Bias tool will be used to assess the risk of bias of the included studies. The random effects model will be used for meta-analyses. The data synthesis will be conducted using Review Manager software (RevMan V.5.3). The Grading of Recommendation, Assessment, Development and Evaluation will be used to assess the quality of supporting evidence for each major comparison. ETHICS AND DISSEMINATION: There is no need for ethical approval. The results of this review will be disseminated through peer-reviewed publications and social networks. PROSPERO REGISTRATION NUMBER: CRD42020165270.

Comparison of iRoot BP Plus and Calcium Hydroxide as Pulpotomy Materials in Permanent Incisors with Complicated Crown Fractures: A Retrospective Study.

INTRODUCTION: Calcium hydroxide has been used as a traditional pulpotomy agent for a long time but has some disadvantages. iRoot BP Plus (Innovative Bioceramix Inc, Vancouver, Canada) is a newly developed, ready-to-use calcium silicate-based bioactive ceramic with excellent bioactivity and sealing ability. However, whether iRoot BP Plus shows superiority over calcium hydroxide as a pulpotomy material on permanent incisors with complicated crown fractures remains unknown. METHODS: This research included 205 permanent incisors with complicated crown fractures. These teeth were treated with pulpotomy and divided into 2 groups according to the pulpotomy material (105 treated with iRoot BP Plus and 100 with calcium hydroxide). Clinical and radiographic information was collected during the 12- to 24-month follow-up period. The formation of reparative dentin bridges and pulp canal obliteration were analyzed using radiographs in both groups. RESULTS: The success rates for recall in the average follow-up period of 17.5 ± 4.4 months (12-24 months) after pulpotomy treatment were significantly different between the 2 groups, with 99% for the iRoot BP Plus group and 93% for the calcium hydroxide group. Reparative dentin bridges were observed in 92.4% of the iRoot BP Plus group and 90% of the calcium hydroxide group, but the difference was not significant. Pulp canal obliteration was observed in 2 teeth (2%) in each group. CONCLUSIONS: The success rates obtained in our study indicate that iRoot BP Plus as a pulpotomy agent can be a suitable alternative to calcium hydroxide to manage complicated crown fractures.

Effects of concentrated growth factor on proliferation, migration, and differentiation of human dental pulp stem cells in vitro.

Concentrated growth factor, a novel autologous plasma extract, contained various growth factors which promoted tissue regeneration. In this study, we aimed to investigate the biological effects of concentrated growth factor on human dental pulp stem cells. The microstructure and biocompatibility of concentrated growth factor scaffolds were evaluated by scanning electron microscopy. Cell proliferation and migration, odontoblastic and endothelial cell differentiation potential were assessed after exposing dental pulp stem cells to different concentrations (5%, 10%, 20%, 50%, or 80%) of concentrated growth factor extracts. The results revealed that concentrated growth factor scaffolds possessed porous fibrin network with platelets and leukocytes, and showed great biocompatibility with dental pulp stem cells. Higher cell proliferation rates were detected in the concentrated growth factor-treated groups in a dose-dependent manner. Interestingly, in comparison to the controls, the low doses (<50%) of concentrated growth factor increased cell migration, alkaline phosphatase activity, and mineralized tissue deposition, while the cells treated in high doses (50% or 80%) showed no significant difference. After stimulating cell differentiation, the expression levels of dentin matrix protein-1, dentin sialophosphoprotein, vascular endothelial growth factor receptor-2 and cluster of differentiation 31 were significantly upregulated in concentrated growth factor-supplemented groups than those of the controls. Furthermore, the dental pulp stem cell-derived endothelial cells co-induced by 5% concentrated growth factor and vascular endothelial growth factor formed the most amount of mature tube-like structures on Matrigel among all groups, but the high-dosage concentrated growth factor exhibited no or inhibitory effect on cell differentiation. In general, our findings confirmed that concentrated growth factor promoted cell proliferation, migration, and the dental pulp stem cell-mediated dentinogenesis and angiogenesis process, by which it might act as a growth factor-loaded scaffold to facilitate dentin-pulp complex healing.

Transplantation of mesenchymal stem cells ameliorates secondary osteoporosis through interleukin-17-impaired functions of recipient bone marrow mesenchymal stem cells in MRL/lpr mice.

INTRODUCTION: Secondary osteoporosis is common in systemic lupus erythematosus and leads to a reduction in quality of life due to fragility fractures, even in patients with improvement of the primary disorder. Systemic transplantation of mesenchymal stem cells could ameliorate bone loss and autoimmune disorders in a MRL/lpr mouse systemic lupus erythematosus model, but the detailed therapeutic mechanism of bone regeneration is not fully understood. In this study, we transplanted human bone marrow mesenchymal stem cells (BMMSCs) and stem cells from exfoliated deciduous teeth (SHED) into MRL/lpr mice and explored their therapeutic mechanisms in secondary osteoporotic disorders of the systemic lupus erythematosus model mice. METHODS: The effects of systemic human mesenchymal stem cell transplantation on bone loss of MRL/lpr mice were analyzed in vivo and ex vivo. After systemic human mesenchymal stem cell transplantation, recipient BMMSC functions of MRL/lpr mice were assessed for aspects of stemness, osteogenesis and osteoclastogenesis, and a series of co-culture experiments under osteogenic or osteoclastogenic inductions were performed to examine the efficacy of interleukin (IL)-17-impaired recipient BMMSCs in the bone marrow of MRL/lpr mice. RESULTS: Systemic transplantation of human BMMSCs and SHED recovered the reduction in bone density and structure in MRL/lpr mice. To explore the mechanism, we found that impaired recipient BMMSCs mediated the negative bone metabolic turnover by enhanced osteoclastogenesis and suppressed osteoblastogenesis in secondary osteoporosis of MRL/lpr mice. Moreover, IL-17-dependent hyperimmune conditions in the recipient bone marrow of MRL/lpr mice damaged recipient BMMSCs to suppress osteoblast capacity and accelerate osteoclast induction. To overcome the abnormal bone metabolism, systemic transplantation of human BMMSCs and SHED into MRL/lpr mice improved the functionally impaired recipient BMMSCs through IL-17 suppression in the recipient bone marrow and then maintained a regular positive bone metabolism via the balance of osteoblasts and osteoclasts. CONCLUSIONS: These findings indicate that IL-17 and recipient BMMSCs might be a therapeutic target for secondary osteoporosis in systemic lupus erythematosus.

LPS-miR-34a-CCL22 axis contributes to regulatory T cell recruitment in periapical lesions.

Regulatory T cells (Tregs) have been shown to regulate the immune response and to control the defense against infection in periapical lesions, but the underlying mechanisms by which Tregs are recruited to these lesions remain unknown. Here we demonstrate that expression of the gene encoding CCL22 (also known as macrophage-derived chemokine), the major chemoattractant that recruits Tregs, is upregulated in periapical tissue during the progression of experimental periapical lesions; this upregulation positively correlated with the number of Tregs that accumulated in the lesions. In terms of mechanism, we determined that lipopolysaccharide (LPS) up-regulates Ccl22 expression in macrophages by suppressing miR-34a. These findings suggest that the LPS-miR-34a-CCL22 axis may contribute to the recruitment of Tregs in periapical lesions, providing a potential therapeutic target for controlling this disease.