A Meta-analysis and Systematic Review Comparing the Effectiveness of Traditional and Virtual Surgical Planning for Orthognathic Surgery: Based on Randomized Clinical Trials.

PURPOSE: To explore the advantages of virtual surgical planning (VSP) and traditional surgical planning (TSP) to determine whether the current VSP technique is superior to the TSP technique for orthognathic surgery. METHODS: An electronic search was carried out in the CENTRAL, PubMed, and Embase databases to identify randomized clinical trials (RCTs) that compared the VSP and TSP techniques regarding their surgical accuracy for hard tissue, prediction precision for soft tissue, required time for planning and surgery, cost and patient-reported outcomes. RESULTS: Eight articles from 5 RCTs, involving 199 patients, were identified. The findings showed that the VSP and TSP techniques were similar in surgical accuracy for hard tissue in the sagittal plane, although the VSP technique was significantly more accurate in certain reference areas, especially in the anterior area of the maxilla. Both the VSP and TSP techniques had significantly better surgical accuracy for the maxilla than for the mandible. The VSP technique showed clinically significantly greater precision for soft tissue prediction in the sagittal plane. Patients who were treated via the VSP technique presented a more symmetrical frontal view, regardless of whether hard or soft tissue was involved. The VSP technique required more time for software planning, but it showed an advantage in time savings when considering the entire preoperative process. Accompanied by the use of an accurate computer-aided splint, the VSP technique could effectively reduce the operative time. Apart from the initial financial investment of software and hardware, the total cost of the VSP technique was similar to that of the TSP technique. Patients who were treated via the VSP or TSP technique showed similar improvements in quality-of-life. CONCLUSIONS: Currently, the VSP technique has become a good alternative to the TSP technique for orthognathic surgery, especially regarding frontal-esthetic considerations. Studies reporting indicators with good representativeness and sensitivity using an identical comparative method are recommended.

Surgical Treatment of Oromandibular Limb Hypogenesis Syndrome Type I A by Distraction Osteogenesis Combined With Orthodontic Rehabilitation.

ABSTRACT: Oromandibular limb hypogenesis syndrome is a rare developmental anomaly and only a few cases are reported with complete surgical and orthodontic rehabilitation. An adult male patient with isolated hypoglossia, micrognathism, hypodontia, (oromandibular limb hypogenesis syndrome type I A) was treated with a combination of distraction osteogenesis and orthodontic intervention. The patient was followed up for the duration of 6 years from his first visit to 4 years after the surgery. The combined procedure resulted in successful and satisfactory treatment of the patient by restoring facial aesthetics, occlusal balance, and functional harmony. However, there was not enough tongue enlargement due to late surgical intervention. The objective of this report is to describe the etiology of hypoglossia, the consequences for oral function, and to share our experience from the oral rehabilitation during the treatment procedure.

Three-Dimensional Cephalometric Analysis: The Changes in Condylar Position Pre- and Post-Orthognathic Surgery With Skeletal Class III Malocclusion.

ABSTRACT: The study includes 21 adult patients with skeletal class III malocclusion who underwent orthognathic surgery and had computed tomography images records presurgery (T0) up to 6 months after the surgery (T1). The computed tomography images were analyzed three-dimensionally using the Proplan CMF 3.0 software. Different skeletal and dental parameters were used in analyzing the cephalometric analysis of the patients. The change in the condylar axis angle was evaluated on 3 planes: axial, coronal, and sagittal. The anteroposterior position of the condyle in relation to the glenoid fossa was evaluated in the sagittal plane. ∠SNB, ∠ANB, ∠Left Y-axis, ∠Right Y-axis were statistically significant (P < 0.01). Significant differences on the condylar axis angle were found between the groups on the sagittal plane (P < 0.05) whereas no significant differences were noted on the axial and the coronal plane. In the anteroposterior condylar position related to the glenoid fossa, the condyle exhibited different displacement on different condyles. The right condyle exhibited more of the posterior displacement whereas the left condyle exhibited more of anterior displacement of the condyle in relation to the glenoid fossa. Numerous studies have done regarding the changes after postsurgery using the two-dimensional cephalometric analysis. Using the 3D techniques helps us to identify the cephalometric point more accurately which thus enhances the accuracy in the cephalometric analysis. However, care should be taken not to change the axis of rotation of the condyle to prevent from the treatment relapse and to avoid temporo-mandibular disorders.

The Influence of the First-Stage DO Treatment of Palate Defect on Growth of Maxilla.

To study the influence of distraction osteogenesis (DO) on the maxillary growth as first-stage treatment of palatal defect. The uniform palate defect experimental animal models (21 miniature pigs) were established surgically. Then animals were randomly divided into negative control group (A, n = 6), conventional surgery group (B, n = 6), and distraction osteogenesis group (C, n = 9) respectively. The group A underwent none treatment as control group, the group B were undergoing a conventional defect repair surgery, and the group C were undergoing a distraction osteogenesis treatment. Cone beam computed tomography examination was performed monthly to analyze the growth of maxilla for 6 months. One pig of group C was randomly sacrificed at 2, 4, and 8 weeks after the completion of DO and the tissue of distraction gap was stained with hematoxylin-eosin and Masson staining. At the end of 6th months, all pigs were sacrificed and tissues of the surgical area were stained as previous described. The palate defect was repaired by the distraction osteogenesis with the successful bone formation on the distraction gap. Group A and group C kept a similar growth rate, but that of group B was relatively slow. Distraction osteogenesis is efficient and successful for closing the defect of palate and there is no significant disturbance on the subsequent growth of the maxilla.

The Soft Tissue Angular Analysis of Facial Profile in Unoperated Adult Patients with Unilateral Cleft Palate.

OBJECTIVE: The purpose of this study was to investigate the differences in facial profile development between unoperated adult cleft palate (UACP) patients and normal controls and to analyse the reasons for the differences. MATERIALS AND METHODS: A total of 50 individuals with a unilateral cleft palate and 20 normal controls were selected to undergo angular measurement of their facial profiles. Data with significant differences between the two groups were analysed. RESULTS: Seven angle measurements of the facial profile showed that the mid-facial protrusion of the UACP patients had no significant differences from the control group (p > 0.05). But their angle of the medium face (N'-Trg-Sn) was significantly lower than the non-cleft controls (p < 0.05), suggesting a worse vertical development of the middle face. A significantly larger nasal tip angle (Cm-Sn/N'-Prn) for UACP patients suggested they had a rounder and blunter nasal tip (p < 0.05). The soft tissue facial angle and chin-lip angle of UACP patients had significant differences from non-cleft controls (p < 0.05), but the head position angle (Sn-Sm-THP) had no significant difference between two groups (p > 0.05), which suggested a steep mandibular plane for UACP patients but without severe retraction of the chin. CONCLUSION: The development of facial protrusions in UACP patients is similar to that in normal adults, but the vertical development in the middle face is insufficient. Such hypoplasia may be related to the intrinsic deficiency of the maxilla. There is a tendency for flat nasal growth and insufficient development of the chin in UACP patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Impact of surgical orthodontic treatment on quality of life in Chinese young adults with class III malocclusion: a longitudinal study.

BACKGROUND: The quality of life in Class III malocclusion patients are worse than those without the disorder and previous studies have shown that surgical orthodontic treatment has a different effect on these patients compared with mild or moderate malocclusion. This study aimed to investigate the changes in quality of life in patients with Class III malocclusion during surgical orthodontic treatment in Chinese young adults. METHODS: The 14-item Short Form Oral Health Impact Profile (OHIP-14), and the 22-item Orthognathic Quality of Life Questionnaire (OQLQ) were used to assess the effect of surgical orthodontic treatment on the quality of life in 21 patients with Class III malocclusion at pre-treatment (T0), pre-surgical orthodontic treatment (6 to 8 months, T1) and post-surgical orthodontic treatment (6 to 8 months after surgery, T2), and 24 healthy individuals were included as controls. The comparisons in numerical variables between patients and controls were performed using Mann-Whitney U test. The scores of the two questionnaires between T0, T1, T2 and controls (Tc) were compared using generalized estimating equation. RESULTS: According to OHIP-14 questionnaire, the mean scores in T0 and T1 were higher than those in T2 and Tc (P < 0.001), and a significant decrease was observed after post-surgical orthodontic treatment (P < 0.001), which achieved a level similar to the control group (P > 0.05). As to OQLQ questionnaire, the mean scores of all domains showed a significant increase between T0 and T1 except for awareness of dentofacial aesthetics (P > 0.05) and social aspects of dentofacial deformity (P > 0.05), followed by a significant decrease between T1 and T2. CONCLUSION: Surgical orthodontic treatment may improve quality of life in patients with Class III malocclusion, but pre-surgical orthodontic treatment may have an adverse effect on quality of life.

Long-Term Skeletal Changes After Maxillary Distraction Osteogenesis in Growing Children With Cleft Lip/Palate.

PURPOSE: To systematically evaluate the skeletal changes after maxillary distraction osteogenesis (DO) in growing patients with cleft lip with or without cleft palate (CL/P). MATERIALS AND METHODS: Electronic databases, gray literature, and reference list searches were conducted. Articles reporting prospective and retrospective studies that included patients <16 years old (N ≥ 6) who had received DO surgery for correction of a midfacial hypoplasia due to CL/P, and the period of follow-up persisted >1 year were reviewed. The original articles were evaluated by 2 investigators to ensure that they met the selection criteria. A methodologic quality assessment tool was used to evaluate the quality of selected studies. Twenty-six studies met the initial search criteria, and 9 articles included 101 growing patients with maxillary hypoplasia due to CL/P who received DO surgery were finally selected and analyzed. RESULTS: The results showed that long term after maxillary advancement with DO, the horizontal relapse in A-point was <15% in 3 studies, 20% to 25% in 1 study, 30% to 35% in 3 studies, and >40% in 1 study. Totally, the range of horizontal relapse in A-point was 11.9% to 45.9%. Similarly, the relapse in SNA angle was <30% in 1 study, 30% to 40% in 3 studies, and >40% in 2 studies. Totally, the range of relapse in SNA was 25.7% to 77%. Two studies showed that the vertical relapse in A-point were 137% and 208%, and in the PNS point were 65% and 62.7%. CONCLUSION: Although findings demonstrated that DO is an effective treatment method for severe maxillary hypoplasia in growing patients with CL/P, there is a relatively high amount of skeletal relapse both in horizontal and vertical dimension. Thus, the first proposed alternative for CL/P patients would be to select the correct primary procedure to decrease damage and avoid unnecessary scars. Then appropriate preoperative and postoperative care is necessary to prevent postoperative relapse. In addition, overcorrection also may be a possible alternative for compensation of postoperative relapse.

Anterior Maxillary Segmental Distraction Osteogenesis for Treatment of Maxillary Hypoplasia in Patients With Repaired Cleft Palate.

OBJECTIVE: This study is to present experiences of using anterior maxillary segmental distraction osteogenesis (AMSDO) with internal distractors for treatment of maxillary hypoplasia in patients with repaired cleft palate. MATERIALS AND METHODS: A total of 42 patients of maxillary hypoplasia with repaired cleft palate were included in this study, and underwent AMSDO. Cephalometric analysis and speech quality assessments were performed to evaluate the changes after AMSDO and its long-term effect on stability. RESULTS: All cases had successfully accomplished AMSDO. The average SNA (°), NA-FH (°), ANS-PNS (millimeter), and Overjet (millimeter) have change to 80.41°, 89.51°, 55.64 mm, and 2.52 mm, respectively (P < 0.01). Maxillary advancement has reached 13.80 mm on average (ranging from 10.0 mm to 20.0 mm). Speech quality assessment demonstrated that nasal resonance, speech articulation, nasal emission, intelligibility, and velopharyngeal function did not get worse after AMSDO. CONCLUSIONS: AMSDO has unique advantages as follows: can effectively correct maxillary hypoplasia in patients with repaired cleft palate; can create a space for postoperative orthodontic treatment to solve the crowding teeth situation; the postoperative velopharyngeal function and speech quality show no significant change. The results shown AMSDO is an effective and appropriate treanment for curing maxillary hypoplasia in patients with repaired cleft palate.

Nonvascularized Free Transport Distraction Osteogenesis to Reconstruct the Mandibular Defect of a Patient With an Ossifying Fibroma: A Case Report.

We report on a case in which trifocal distraction osteogenesis was applied in a patient with a mandibular defect caused by resection of an ossifying fibroma. During the surgical procedure, we accidentally dissected the surrounding periosteal tissue of the left transport completely in the process of transport disc preparation and made the disc into a free bone graft. However, we still used this transport and successfully completed the distraction osteogenesis. The patient's facial and occlusal function were regained after treatment.

Dynamic Analysis of New Bone Obtained by Nonvascular Transport Distraction Osteogenesis in Canines.

PURPOSE: The aim of the present study was to construct a nonvascular transport disc to repair the canine mandibular defects model and to perform a dynamic analysis of the new bone obtained by nonvascular transport distraction osteogenesis (NTDO) in canines. MATERIALS AND METHODS: Thirty adult dogs were randomly divided into 3 groups, with 10 dogs in each group. Canine mandibular defect models of NTDO were constructed. All the dogs were marked by tetracycline hydrochloride at a different distraction stage. The dogs were euthanized at 2, 4, and 12 weeks after distraction, and the quality ratio of calcium and phosphate for the new bone was measured using electron dispersive spectroscopy. RESULTS: The canine mandibular defects were successfully repaired. Using tetracycline hydrochloride, we successfully observed the quality and speed of new bone formation. The quality ratio of calcium and phosphate was similar between the new bone formation and the original bone. The time spent using a nonvascular transport disc to repair mandibular defects was consistent with using a vascularized transport disc, and the quality of the new bone and the original bone was exactly the same. CONCLUSION: When the bone mass is insufficient or the conditions are not suitable for a vascularized transport disc, the nonvascular transport disc can be used as an alternative.

A new classification of mandible defects and condyle changed after mandible reconstruction with FFF.

Objectives: To explore a new classification of mandibular defects and changes in the preserved condyle after mandibular reconstruction with free fibular flap(FFF). Study design: We reviewed patients who underwent mandibular reconstruction with FFF from 2015 to 2021 and classified the mandibular defects into five categories: classⅠ(unilateral-mandibular excluding condyle), classⅡ(unilateral-mandibular including condyle), classⅢ(bilateral-mandibular excluding condyle), classⅣ(bilateral-mandibular including one condyle), and classⅤ(bilateral-mandibular including both condyles). Cone Beam Computed Tomography (CBCT) data were collected preoperatively(T0), at 7-10 postoperative days(T1), 6 postoperative months(T2), and 1 postoperative year(T3). We calculated the condylar surface area, volume, and displacement. Results: 62 cases were collected. The condylar surface areas and volumes in T2 and T3 values were lower than those of T0 and T1(P < 0.01) The condylar displacement was the lowest in ClassI and the largest in ClassⅣ(P < 0.01), while no significant differences in classesⅠ-Ⅲ(P < 0.05). Displacement during T1-T0 was greater than that during T2-T0 and T3-T0(P < 0.05). Conclusion: Mandibular reconstruction with FFF results in displacement and alteration of the condyle within a time interval, and this alteration stabilizes after 6 months. Mandibular defects that do not reach the midline, surgical alteration to preserve the condyle are not required. However, when the defects cross the midline, the condyle should be preserved as much as possible.

Effect of surgery-first approach on quality of life and mental health of orthognathic patients: A systematic review and meta-analysis.

Objectives: This study intends to explore the effects of the surgery-first approach (SFA) on quality of life and mental health of patients who undergo orthognathic surgery compared to the conventional three-stage approach (CTA). Data: The analysis included eight studies with a total of 307 patients, of which one was randomized controlled trial (RCT), one was clinical controlled trial (CCT), and six were non-randomized studies of interventions (NRSIs). Sources: Electronic databases such as Medline, Embase, Scopus, and Web of Science were searched for eligible trials up to April 2023. Study selection: RCTs, CCTs, and NRSIs, which compared the quality of life or mental health of orthognathic patients treated with SFA and CTA, were included in this study. The meta-analysis showed that the standardized mean differences (SMD) of Oral Health Impact Profiles-14 (OHIP-14) scores and the Orthognathic Quality of Life Questionnaire (OQLQ) between SFA and CTA were -1.58 (P = 0.05) and -2.99 (P < 0.00001) at the termination of the first-stage treatment, which altered to -0.94 (P = 0.54) and 0.09 (P = 0.65) after total treatment. Two studies applied the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) and the Beck Depression Inventory (BDI-II) to examine mental health, resulting in a trend similar to the former scales. Conclusion: In contrast to the conventional procedure, orthognathic treatment with SFA can instantly enhance the quality of life at the end of the first-stage treatment but has similar effects after the overall treatment. Moreover, SFA has a positive impact on psychological conditions. Clinical significance: This study first systematically reviewed the effect of SFA on patients' mental well-being. According to our findings, it is better to select SFA if possible. Otherwise, the patient's psychological condition should be monitored appropriately throughout decompensation for better well-being both physically and mentally.

Mandibular reconstruction after excision of recurrent odontogenic keratocyst using a novel mandibular distraction osteogenesis method- a case report.

BACKGROUND: Odontogenic keratocyst is one of the most common benign odontogenic neoplasms with a high recurrence rate. Its resection has the potential to lead to mandibular segmental defects. In this case report, we describe a patient with odontogenic keratocyst who underwent radical resection using a novel distraction osteogenesis (DO) method to reconstruct mandibular segmental defect. CASE PRESENTATION: This case report describes a 19-year-old woman with odontogenic keratocyst of the mandible that recurred after multiple curettages and eventually necessitated radical resection. Mandibular segmental defect after radical resection was reconstructed using a novel DO method that involved directly contacting the segment ends of the defect without the transport disk. However, the distractor broke during the retention period, and a molding titanium plate was used for fixation. This novel distraction method achieved mandibular reconstruction and restored mandibular function and contour.

Three-dimensional analysis of the morphological changes of the craniofacial jaw and condyle in patients with idiopathic condylar resorption.

In this study we aim to describe the three-dimensional analysis of condylar deformation of the temporomandibular joint (TMJ) and morphological changes of the craniofacial jaw in patients with idiopathic condylar resorption (ICR). We also compare those with a control group that is healthy and matched for age and gender. Cone-beam computed tomography (CBCT) and cephalometric radiograph (X-ray) were conducted and analysis of craniofacial measurement, condylar width, length, height, and condylar axial angle changes were done three-dimensionally using ProPlan CMF™ 3.0 software (Materialise). The craniofacial jaw measurements of the ICR patients were significantly different than the control group and the significant changes in the mandible can be seen in ICR patients according to the results of this study. The results of smaller condylar width and height in the ICR group reflect the smaller size of the condyle compared with an unaffected condyle. Also, both right and left sagittal condylar angles (p = 0.001 and p = 0.003), respectively, and axial condylar angles (p = 0.01 and p = 0.02), respectively, displayed significant differences between the two groups. In conclusion, the vertical development of the condyle decreased along with reduced measurements in the width and height of the condyle in ICR patients, and differences in the morphology of the craniofacial jaw and condylar angles were observed between study groups.

Correlation analysis of upper airway morphology in patients with obstructive sleep apnea and anatomically small retruded mandibles.

OBJECTIVE: To investigate the relationship between upper airway morphology and the severity of obstructive sleep apnea (OSA) in patients with anatomically small retruded mandibles. METHODS: Fifty-two patients with small retruded mandibles underwent polysomnography and airway computed tomography. The airway morphology parameters and sleep assessment were compared between the patients with or without OSA. RESULTS: Twenty-eight patients diagnosed with OSA, according to polysomnography, had a higher distance between the hyoid bone and mandibular plane (HMP), lateral dimension (LAT)/anteroposterior dimension (AP), but lower minimum cross-sectional area (mCSA), AP, surface area, volume, avgCSA, and airway uniformity (U). The apnea-hypopnea index had negative correlations with mCSA, AP, surface area, volume, avgCSA, and U, and had a positive correlation with HMP and LAT/AP. CONCLUSION: OSA is common among patients with small retruded mandibles and is associated with a more compressed upper airway shape and longer HMP.

A natural biomineral for enhancing the biomineralization and cell response of 3D printed polylactic acid bone scaffolds.

Polylactic acid (PLA) has been extensively used as a bone scaffold material, but it still faces many problems including low biomineralization ability, weak cell response, low mechanical properties, etc. In this study, we proposed to utilize the distinctive physical, chemical and biological properties of a natural biomineral with organic matrix, pearl powder, to enhance the overall performance of PLA bone scaffolds. Porous PLA/pearl composite bone scaffolds were prepared using fused deposition modeling (FDM) 3D printing technology, and their comprehensive performance was investigated. Macro- and micro- morphological observation by the optical camera and scanning electron microscopy (SEM) showed the 3D printed scaffolds have interconnected and ordered periodic porous structures. Phase analysis by X-ray diffraction (XRD) indicated pearl powder was well composited with PLA without impurity formation during the melt extrusion process. The mechanical test results indicated the tensile and compressive strength of PLA/pearl composite scaffolds with 10 % pearl powder content yielded the highest values, which were 15.5 % and 21.8% greater than pure PLA, respectively. The water contact angle and water absorption tests indicated that PLA/pearl showed better hydrophilicity than PLA due to the presence of polar groups in the organic matrix of the pearl powder. The results of the simulated body fluid (SBF) soaking revealed that the addition of pearl powder effectively enhanced the formation and deposition of apatite, which was attributed to the release of Ca2+ from the dissolution of pearl powder. The cell culture of bone marrow mesenchymal stem cells (BMSCs) indicated that PLA/pearl scaffolds showed better cell proliferation and osteogenic differentiation than PLA due to the stimulation of the biological organic matrix in pearl powder. These outcomes signify the potential of pearl powder as a natural biomineral containing bio-signal factors to improve the mechanical and biological properties of polymers for better bone tissue engineering application.

Promotion of osteogenesis in BMSC under hypoxia by ATF4 via the PERK-eIF2α signaling pathway.

Mandibular distraction osteogenesis (MDO) is an endogenous tissue engineering technology in which bone marrow mesenchymal stem cells (BMSC) play a key role in MDO-related osteogenesis. Activating transcription factor 4 (ATF4) is involved in osteogenesis through activation of PERK (Protein kinase R-like endoplasmic reticulum kinase) in endoplasmic reticulum stress (ERS) condition under hypoxia. However, the specific role of ATF4 in MDO with BMSC remains unknown. The aim of this study was to explore the effects of ATF4 in MDO with BMSC under hypoxia. Briefly, canine BMSCs were cultured in a hypoxic chamber, and effects of hypoxia were evaluated using cell migration assay and Alizarin Red S staining. Expression levels of protein kinase R-like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2α, ATF4, osteocalcin, and bone sialoprotein were evaluated using quantitative polymerase chain reaction and western blotting. BMSCs were transduced with the ATF4-small interfering RNA lentivirus. The effects were evaluated using all the aforementioned experiments. The results showed that hypoxia promoted migration, osteoblast differentiation, and ATF4 expression in BMSC. ATF4 knockdown in BMSC significantly inhibited migration and osteoblast differentiation abilities, while hypoxia reversed these effects to some extent. In addition, the molecular mechanism partly depended on the ERS signaling pathway, with ATF4 as the key factor. In summary, we presented a novel mechanism of ATF4-mediated regulation of BMSC under hypoxia.

Hsp20 Promotes Endothelial Progenitor Cell Angiogenesis via Activation of PI3K/Akt Signaling Pathway under Hypoxia.

BACKGROUND: Mandibular distraction osteogenesis (MDO) is a kind of endogenous tissue engineering technology that lengthens the jaw and opens airway so that a patient can breathe safely and comfortably on his or her own. Endothelial progenitor cells (EPCs) are crucial for MDO-related angiogenesis. Moreover, emerging evidence suggests that heat shock protein 20 (Hsp20) modulates angiogenesis under hypoxic conditions. However, the specific role of Hsp20 in EPCs, in the context of MDO, is not yet known. The aim of this study was to explore the expression of Hsp20 during MDO and the effects of Hsp20 on EPCs under hypoxia. METHODS: Mandibular distraction osteogenesis and mandibular bone defect (MBD) canine model were established. The expression of CD34, CD133, HIF-1α, and Hsp20 in callus was detected by immunofluorescence on day 14 after surgery. Canine bone marrow EPCs were cultured, with or without optimal cobalt chloride (CoCl2) concentration. Hypoxic effects, caused by CoCl2, were evaluated by means of the cell cycle, cell apoptosis, transwell cell migration, and tube formation assays. The Hsp20/KDR/PI3K/Akt expression levels were evaluated via immunofluorescence, RT-qPCR, and western blot. Next, EPCs were incorporated with either Hsp20-overexpression or Hsp20-siRNA lentivirus. The resulting effects were evaluated as described above. RESULTS: CD34, CD133, HIF-1α, and Hsp20 were displayed more positive in the callus of MDO compared with MBD. In addition, hypoxic conditions, generated by 0.1 mM CoCl2, in canine EPCs, accelerated cell proliferation, migration, tube formation, and Hsp20 expression. Hsp20 overexpression in EPCs significantly stimulated cell proliferation, migration, and tube formation, whereas Hsp20 inhibition produced the opposite effect. Additionally, the molecular mechanism was partly dependent on the KDR/PI3K/Akt pathway. CONCLUSION: In summary, herein, we present a novel mechanism of Hsp20-mediated regulation of canine EPCs via Akt activation in a hypoxic microenvironment.

Identification of the key exosomal lncRNAs/mRNAs in the serum during distraction osteogenesis.

BACKGROUND: Distraction osteogenesis (DO), a kind of bone regenerative process, is not only extremely effective, but the osteogenesis rate is far beyond ordinary bone fracture (BF) healing. Exosomes (Exo) are thought to play a part in bone regeneration and healing as key players in cell-to-cell contact. The object of this work was to determine whether exosomes derived from DO and BF serum could stimulate the Osteogenic Differentiation in these two processes, and if so, which genes could be involved. METHODS: The osteogenesis in DO-gap or BF-gap was evaluated using radiographic analysis and histological analysis. On the 14th postoperative day, DO-Exos and BF-Exos were isolated and cocultured with the jaw of bone marrow mesenchymal stem cells (JBMMSCs). Proliferation, migration and osteogenic differentiation of JBMMSCs were ascertained, after which exosomes RNA-seq was performed to identify the relevant gene. RESULTS: Radiographic and histological analyses manifested that osteogenesis was remarkably accelerated in DO-gap in comparison with BF-gap. Both of the two types of Exos were taken up by JBMMSCs, and their migration and osteogenic differentiation were also seen to improve. However, the proliferation showed no significant difference. Finally, exosome RNA-seq revealed that the lncRNA MSTRG.532277.1 and the mRNA F-box and leucine-rich repeat protein 14(FBXL14) may play a key role in DO. CONCLUSIONS: Our findings suggest that exosomes from serum exert a critical effect on the rapid osteogenesis in DO. This promoting effect might have relevance with the co-expression of MSTRG.532277.1 and FBXL14. On the whole, these findings provide new insights into bone regeneration, thereby outlining possible therapeutic targets for clinical intervention.

microRNA-146a mediates distraction osteogenesis via bone mesenchymal stem cell inflammatory response.

Distraction osteogenesis (DO) is a widely used surgical technique to repair bone defects, partly owing to its high efficiency in inducing osteogenesis; however, the process of osteogenesis is complex, and the precise mechanism is still unclear. Among the factors identified for an effective DO procedure, well-controlled inflammation is essential. We aimed to explore how microRNA(miR)-146a, a negative regulator of inflammation, influences osteogenesis in DO. First, we established canine right mandibular DO and bone fracture models to evaluate the expression level of miR-146a in response to these procedures. Second, bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy puppies and cultured with lipopolysaccharide (LPS) to observe how inflammation affects osteogenesis. Finally, the osteogenesis activity of BMSCs transfected with lentiviral vector either overexpressing (miR-146a-up) or inhibited for miR-146a expression was evaluated. miR-146a-up-transfected BMSCs were injected locally into the distraction gaps of the DO model canines. On days 42 and 56 post-surgery, the bone volume/tissue volume and bone mineral density values were evaluated via using micro-computed tomography, and newly formed tissues were harvested and evaluated via histological staining. The expression of miR-146a in both the DO canine model and LPS-stimulated BMSCs increased. Overexpression of miR-146a enhanced cell proliferation, migration, and osteogenic differentiation. Additionally, the newly formed callus was improved in canine mandibles injected with miR-146a-up-transfected BMSCs. In summary, miR-146a regulates mandibular DO by improving osteogenesis, and can serve as a potential target to shorten the therapy period of DO.