BACKGROUND:Osteoarthritis,often accompanied by cartilage abnormal signal transduction,suggesting that intracellular signal transduction may play an important role in osteoarthritis genesis and development.OBJECTIVE:To review recent advances in the research of Notch signaling pathway,and explore the mechanisms of chondrogenic differentiation of bone marrow mesenchymal stem cells and its role in cartilage development and chondrogenesis.To analysis the role of dysregulated Notch signaling in the development of osteoarthritis.METHODS:Pubmed was undertaken to identify the relevant articles published from March 1919 to February 2009 with the key words of"Notch signaling pathway,osteoarthritis,chondrocytes,chondrogenesis,bone marrow stem cells"in English.Simultaneously,CNKI Database was searched for relevant articles published from February 2004 to September 2008 with the key words of"Notch signaling pathway,osteoarthritis,chondrocytes,chondrogenesis,bone marrow stem cells"in Chinese Articles with the Notch signaling pathway-related research,Notch signaling pathway of bone marrow-derived mesenchymal stem cells,differentiation of cartilage relative to the mechanism studies,and the Notch signaling pathway disorders and osteoarthritis research were included,Reproducibility articles were excluded Development regulation of articular cartilage and cartilage cell proliferation were considered as evaluation indexes.RESULTS AND CONCLUSION:Of 632 articles retrieved,30 were included in our study according to the inclusive and exclusive criteria.The Notch pathway is a highly consewed signaling mechanism involved in many processes determining cell fate during development and maintenance of homeostasis of mature tissues in the adult organism.Activation of Notch occurs following Notch receptor/ligand engagement upon cell-cell contact,which initiates translocation of the Notch intracellular domain to the nucleus and activation of target genes.It has been demonstrated that the Notch signaling plays an important role in regulating articular cartilage development and chondrocyte proliferation and differentiation In recent studies abnormality of notch signaling was also found in disease,which suggests that notch signaling is involved in osteoarthritis initiation and development.Further study of the specific mechanism of notch signaling in the initiation and development of osteoarthritis will enable us to develop targeted approaches in the treatment of osteoarthritis,thus bring more strategies in the future treatment of osteoarthritis.

OBJECTIVEThis work investigated mesenchymal stem cells (MSCs) modified with Runt-related transcription factor 2 (Runx2) therapy for bone regeneration in rabbit mandibular distraction osteogenesis.

METHODSForty-eight New Zealand mature white rabbits were randomly divided into three groups after the rabbit model of mandibular distraction osteogenesis was established: reconstruction plasmid modified with Runx2 (group A), plasmid without Runx2 (group B), and the same dose of saline as control (group C). At the fifth day of distraction phase, MSCs with reconstruction plasmid modified with adv-hRunx2-gfp were injected into the distraction gap of group A. MSCs with reconstruction plasmid modified with adv-gfp was injected into the distraction gap of group B, whereas group C was injected with the same dose of saline. At 8 weeks after injection, all animals were sacrificed, and the distracted mandibles were harvested. The general imaging histological observation and three-point bending test were used for evaluation.

RESULTSCT plain scan and histological analysis confirmed that the amount of new bone forming in the distraction gap of group A was significantly higher than those in groups B and C. Dual-energy X ray and three-point bending test results also showed that the bone mineral density, bone mineral content, and maximum load of the distraction gap of group A were significantly higher than those of groups B and C (P<0.01).

CONCLUSIONRunx2-ex vivo gene therapy based on MSCs can effectively promote the bone regeneration in rabbit mandibular distraction osteogenesis and shorten the stationary phase. Therefore, reconstruction of craniofacial fracture would be a valuable strategy

Absorptiometry, Photon ; Animals ; Bone Density ; Bone Regeneration ; physiology ; Core Binding Factor Alpha 1 Subunit ; genetics ; pharmacology ; Genetic Therapy ; Mandible ; physiology ; surgery ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; Osteogenesis ; genetics ; Osteogenesis, Distraction ; methods ; Plasmids ; Rabbits ; Random Allocation ; Transcription Factors ; genetics ; physiology ; Treatment Outcome

Objective To assess the value of contrast-enhanced ultrasonography (CEUS ) in diagnosing BI-RADS 4 breast lesion.Methods The CEUS findings of 79 breast lesions of BI-RADS 4 were analyzed,and the CEUS diagnosis was made according to our preliminary study results.Histology results were served as golden reference.Results Of all the 79 breast lesions that were confirmed by histopathology results,36 were malignant and 43 were benign.The differences of morphologic features of area variety, margin,heterogeneous or homogeneous distribution between benign and malignant lesions were significant (P < 0.05 ).The area under ROC curve of correction BI-RADS classification in the diagnosis of breast cancer was 0.938,and it was significantly higher than that of the BI-RADS classification (0.889,Z =2.209, P =0.0272).Conclusions CEUS can improve the diagnostic accuracy of breast lesions preoperatively.

Objective:To introduce a 2-stage treatment protocol for the management of temporomandibular joint ankylosis with sec-ondary deformities in adults.Methods:24 adult patients (9 males and 15 female)(30 joints)at the average age of 26.1 years un-derwent TMJ reconstruction as the initial surgery,followed by orthodontic treatment and correction of secondary deformities as the sec-ond surgery.Clinical outcome was assessed based on maximal incisal opening,radiography and medical photography.Results:Skele-tal deformities were significantly improved in all patients,satisfactory occlusion was achieved with the orthodontic treatment,average maximal incisal opening increased from 3.4 mm to 32.5 mm(P <0.05).Conclusion:The 2-stage treatment protocol is an effective approach for management of TMJ ankylosis with secondary deformities in adult patients.

BACKGROUND:During the healing of fractures, removal of sciatic nerve can result in insufficient mechanical rigidity of newborn woven bone. However, there are less reports concerning the denervation effects during distraction osteogenesis. OBJECTIVE:To observe the effect of removal of the sciatic nerve on bone regeneration and the expression of Runt-related transcription factor 2 (Runx2) protein during distraction osteogenesis in a rabbit model. METHODS:Twenty-four adult male New Zealand rabbits were selected and underwent left tibial osteodistraction to construct animal models of distraction osteogenesis. Before distraction, the animals were randomly divided into group R (resecting the left sciatic nerve) and group I (intact left sciatic nerve). Six weeks after completion of distraction, the animals were kil ed and the lengthened tibias were harvested for radiography, three-dimensional CT reconstruction, histological evaluation, connectivity density (Conn.D) evaluation. RESULTS AND CONCLUSION:New regenerated bone was present and Runx2 protein was expressed in the distraction gaps of al animals at the end of the study, as revealed by radiography, three-dimensional CT reconstruction, and histological observation. However, less new bone formation and a lower degree of mineralization and expression of Runx2 protein were observed in group R compared with group I. The results suggest that the denervation appears to have an inhibitory effect on bone formation and the expression of Runx2 protein during distraction osteogenesis.

Orthognathic surgery and temporomandibular joint (TMJ) surgery are two relatively independent disciplines in oral and maxillofacial surgery. Dentofacial deformities and TMJ diseases commonly coexist. The diagnosis and treatment of the diseases with coexisting dentofacial deformities and TMJ disorders is complex. Thus it is very important to comprehensively understand the common characteristics of orthognathic and TMJ surgery, which places a greater demand on oral and maxillofacial surgeons. The present work focuses on our thinking on common characteristics of TMJ and orthognathic surgery based on the managements of these diseases.

Dento-maxillofacial deformity refers to an abnormal relationship of the volume or shape of the upper and lower jaw bones with the other bones of the craniofacial area. Its correction mainly involves hard tissues, such as the jaws and teeth. In recent years, digital techniques based on virtual surgery, real-time navigation, and 3D printing have developed rapidly in the area of craniomaxillofacial surgery. Digital technology has advantages for preoperative diagnosis, surgical plan formulation, surgical simulation, intraoperative navigation, effect prediction, doctor-patient communication, and young physician training. The Department of Orthognathic and TMJ Surgery of West China Hospital of Stomatology, Sichuan University, has conducted digitized diagnosis and treatment of dento-facial deformities since 2008 and has established a digital center for the treatment of dentofacial deformities based on equipment such as spiral CT, dental arch laser scanners, facial 3D cameras, virtual surgery software, 3D printers, and sleep-breathing monitoring. The result is a diagnostic and treatment protocol for dentofacial deformity specific to the characteristics of the population of West China. This article combines the latest domestic and foreign literature and comprehensively introduces the application of digital technology for the diagnosis and treatment of dental and maxillofacial deformities.

The teaching of orthognathic surgery is difficult because it is complex and emphasizes the combination of theory and practice. The traditional teaching method focuses on theoretical teaching, but due to the limitation of conditions, it is difficult for students to master the operation. In this paper, we apply the digital three-dimensional surgical simulation system combined with 3D printing in specialist training of orthognathic surgery. Digital software and 3D printing are applied in the theoretical teaching, surgical operation, summary and reflection to combine practical teaching with theoretical teaching, so as to stimulate the subjective initiative of the students. The results showed that the teaching evaluation of the experimental group [(3.89±0.84) points] was better than that of the control group [(2.91±1.21) points]. The application of digital three-dimensional surgical simulation system combined with 3D printing has achieved satisfactory results.

Objective : To design a novel biomimetic micro/nano hierarchical interface on endosseous titanium implants and investigate its effect on the biological activity of bone marrow mesenchymal cells. Methods: Electrochemical anodization and spark plasma sintering were used to modify smooth titanium (untreated Ti group) with a microporous trabecular bone-like architecture (micro-Ti group) and TiO2 nanotube architecture (nano-TiO2 group). Additionally, electrochemical anodization was employed to prepare TiO2 nanotubes on microporous trabecular bone-like architectures, which formed a novel biomimetic hierarchical interface (micro/nano-TiO2 group). Four groups of titanium samples were characterized by field emission scanning electron microscopy (SEM), atomic force microscopy (AFM) and contact angle (CA). Bone marrow mesenchymal cells (BMMCs) were seeded on four groups of titanium samples. Scanning electron microscopy (SEM) was employed to observe cell morphology. Cell proliferation was determined by MTT assay. The expression of focal adhesion proteins (F-actin; vinculin; osteocalcin, OCN; osteopontin, OPN) were observed under a confocal laser scanning microscope (CLSM). The mRNA expression levels of osteogenic factors (runt-related transcription factor 2, RUNX2; osteocalcin, OCN; osteopontin, OPN; collagen I, COL I) were assessed by qRT-PCR. Results: The micro/nano- TiO2 group featured a hydrophilic surface (CA=9° ± 2.1°). The results of the MTT assay indicated that the relative cell proliferation rates for the nano- TiO2 and micro/nano-TiO2 samples were significantly increased compared with those for the untreated-Ti and micro-Ti samples (P＜0.001) after 5-9 days. The ALP results indicated that the micro/nano-TiO2 sample gained the highest value at 14 days. After 72 h of incubation, the expression of osteocalcin (OCN) and osteopontin (OPN) on micro/nano-TiO2 was the strongest. After 24 h incubation, the expression of F-actin on micro/nano-TiO2 was the strongest. In comparison with untreated-Ti and micro-Ti samples,the mRNA expression levels of all the osteogenic factors (runt-related transcription factor 2, RUNX2; osteocalcin, OCN; osteopontin, OPN; Collagen I, COL I) were markedly increased on the nano-TiO2 and micro/nano-TiO2 samples, the mRNA expression levels of collagen I (COL I) were significantly different between the nano-TiO2 and micro/nano-TiO2 samples versus the untreated-Ti and micro-Ti samples (P＜0.001). Conclusion The novel biomimetic micro/nano hierarchical interface has a positive effect on cell attachment, viability and osteogenic differentiation of bone marrow mesenchymal cells.

Objective: To provide a clinical reference by evaluating the precision of virtual surgical planning in two⁃ jaw orthognathic surgery. Methods : Thirty consecutive patients who required two⁃jaw orthognathic surgery were includ⁃ ed. A composite skull model was reconstructed using data from spiral computed tomography scan and surface scanning of the dental arch. LeFort I osteotomy of the maxilla and bilateral sagittal split ramus osteotomy of the mandible were simulated using Dolphin Imaging 11.7 Premium. Genioplasty was performed if indicated. Virtual plan was then trans⁃ ferred to operation room using 3D⁃printed surgical templates. Frankfort horizontal plane (FHP), midfacial plane (perpen⁃ dicular to the FHP through the nasion), and coronal plane (perpendicular to the FHP through the sella point) were the selected three symmetry planes.Midpoint of the contact of the maxillary and mandibular central incisors (UI, LI), and the mesio⁃buccal cusp of the first maxillary and mandibular molars (U6⁃R,U6⁃L, L6⁃R, L6⁃L) were the six chosen volu⁃metric landmarks. To calculate the linear difference and overall mean linear difference (mean difference of the distance between UI, LI, U6⁃R, U6⁃L, L6⁃R, L6⁃L to FHP, midfacial and coronal plane) between simulated and postoperative models, the distance between selected landmarks and symmetry planes was measured. To calculate the angular differ⁃ ence and overall mean angular difference, values of the angles constructed by the occlusal, palatal, and mandibular plane to FHP and midfacial plane respectively were determined on simulated and postoperative models Results: The virtual surgical planning was successfully transferred to actual surgery with the help of 3D⁃printed surgical templates. All patients were satisfied with the postoperative facial profile and occlusion. The overall mean linear difference was 0.81 mm (0.71 mm for maxilla and 0.91 mm for mandible); and the overall mean angular difference was 0.95° (the mean angular difference relative to FHP was 1.10°, and that relative to midfacial plane was 0.83°) Conclusion Virtual sur⁃ gical planning facilitated the diagnosis, treatment planning, and precise bony segments repositioning in two⁃jaw orthog⁃ nathic surgery.