p75NTR-/- mice exhibit an alveolar bone loss phenotype and inhibited PI3K/Akt/β-catenin pathway.
- 作者列表："Wang Y","Yang K","Li G","Liu R","Liu J","Li J","Tang M","Zhao M","Song J","Wen X
OBJECTIVES:The aim of this study was to investigate the role of p75 neurotrophin receptor (p75NTR) in regulating the mouse alveolar bone development and the mineralization potential of murine ectomesenchymal stem cells (EMSCs). Moreover, we tried to explore the underlying mechanisms associated with the PI3K/Akt/β-catenin pathway. MATERIALS AND METHODS:p75NTR knockout (p75NTR-/- ) mice and wild-type (WT) littermates were used. E12.5d p75NTR-/- and WT EMSCs were isolated in the same pregnant p75NTR-/+ mice from embryonic maxillofacial processes separately. Mouse alveolar bone mass was evaluated using micro-CT. Differential osteogenic differentiation pathways between p75NTR-/- and WT EMSCs were analysed by RNA-sequencing. The PI3K inhibitor LY294002 and PI3K agonist 740Y-P were used to regulate the PI3K/Akt pathway in EMSCs. p75NTR overexpression lentiviruses, p75NTR knock-down lentiviruses and recombined mouse NGF were used to transfect cells. RESULTS:The alveolar bone mass was found reduced in the p75NTR knockout mouse comparing to the WT mouse. During mineralization induction, p75NTR-/- EMSCs displayed decreased osteogenic capacity and downregulated PI3K/Akt/β-catenin signalling. The PI3K/Akt/β-catenin pathway positively regulates the potential of differential mineralization in EMSCs. The promotive effect of p75NTR overexpression can be attenuated by LY294002, while the inhibitory effect of p75NTR knock-down on Runx2 and Col1 expression can be reversed by 740Y-P. CONCLUSION:Deletion of p75NTR reduced alveolar bone mass in mice. P75NTR positively regulated the osteogenic differentiation of EMSCs via enhancing the PI3K/Akt/β-catenin pathway.
目的: 本研究旨在探讨p75 神经营养因子受体 (p75NTR) 在调节小鼠牙槽骨发育和小鼠外胚间充质干细胞 (EMSCs) 矿化潜能中的作用。此外，我们试图探索与PI3K/Akt/β-catenin通路相关的潜在机制。 材料和方法: 采用p75NTR基因敲除 (p75NTR-/-) 小鼠和野生型 (WT) 同窝小鼠。E12.5d p75NTR-/-和WT EMSCs分别在来自胚胎颌面突的同一妊娠p75NTR-/+ 小鼠中分离。使用micro-CT评价小鼠牙槽骨量。通过RNA测序分析p75NTR-/-和WT EMSCs之间的差异成骨分化途径。用PI3K抑制剂LY294002 和PI3K激动剂 740Y-P调控EMSCs中PI3K/Akt通路，p75NTR过表达慢病毒、p75NTR敲低慢病毒和重组小鼠NGF转染细胞。 结果: 与WT小鼠相比，p75NTR基因敲除小鼠牙槽骨量减少。矿化诱导过程中，p75NTR-/- EMSCs显示成骨能力下降，PI3K/Akt/β-catenin信号下调。PI3K/Akt/β-catenin通路正调控EMSCs差异矿化的潜力。LY294002 可减弱p75NTR过表达的促进作用，而 740Y-P可逆转p75NTR敲低对Runx2 和Col1 表达的抑制作用。 结论: p75NTR缺失可减少小鼠牙槽骨量。P75NTR通过增强PI3K/Akt/β-catenin通路正调控EMSCs的成骨分化。
METHODS:BACKGROUND:The anterior oronasal fistulae neighboring the alveolar cleft could persist or reappear after the alveolar reconstruction with cancellous bone grafting. The persistent symptomatic anterior oronasal fistulae need to be repaired, but surgery remains a challenge in cleft care. Surprisingly, this issue has rarely been reported in the literature. The purpose of this long-term study was to report a single surgeon experience with a therapeutic protocol for persistent symptomatic anterior oronasal fistula repair. METHODS:This is a retrospective study of consecutive patients with Veau type III and IV clefts and persistent symptomatic anterior oronasal fistulae managed according to a therapeutic protocol from 1997 to 2018. Depending on fistula size, patients were treated with local flaps associated with an interpositional graft or two-stage tongue flaps (small/medium or large fistulae, respectively). The surgical outcomes were classified as "good" (complete fistula closure with no symptoms), "fair" (asymptomatic narrow fistula remained), or "poor" (failure with persistent symptoms). RESULTS:Forty-four patients with persistent symptomatic anterior oronasal fistulae were reconstructed with local flaps associated with interpositional fascia or dermal fat grafting (52.3%) or two-stage tongue flaps (47.7%). Most of patients (93.2%) presented "good" outcomes, ranging from 87% to 100% (local and tongue flaps, respectively). Three (6.8%) patients presented symptomatic residual fistula ("poor" outcomes). CONCLUSIONS:For the repair of persistent symptomatic anterior oronasal fistulae, this therapeutic protocol provided satisfactory outcome with low fistula recurrence rate.
METHODS:OBJECTIVE:Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS. DESIGN/SETTING:This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995-2011. PATIENTS:Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks' gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview. RESULTS:Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1-12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2). CONCLUSIONS:These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk-benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.
METHODS::Orthopedic treatment to improve deficient maxillary growth of cleft lip and palate patients is an important part of treatment. The success of this treatment is strongly dependent on the time of initiation of therapy. There has been a large controversy in the available literature regarding the skeletal age of these patients. The aim of the present study was to compare the skeletal age of cleft lip and palate patients with normal individuals.37 unilateral and 14 bilateral cleft lip and palate patients and 47 healthy individuals participated in this cross-sectional study. The patients were classified into 8 to 10 and 11 to 14-year-old individuals. Cervical vertebral maturational stage of participants was evaluated in the lateral cephalometry. The skeletal age of cleft lip and palate patients was compared with normal controls. Chi-square was used for statistical analysis. There was not a significant difference in the skeletal developmental stage of unilateral and bilateral cleft compared to their normal peers according to their age and sex. Also, significant difference in skeletal maturational stage of cleft lip and palate patients was not found between boys and girls (P = 0.8). Similarly, no significant difference was found in the skeletal age of the 3 studied groups without considering the age and sex of participants (P = 0.5). Regarding the similar skeletal maturational stage of cleft lip and palate patients with normal controls in our study, their maxillofacial orthopedic treatment can be initiated at similar time to normal peers.