The accuracy of three-dimensional rapid prototyped surgical template guided anterior segmental osteotomy

Surgical guiding templates provided a reliable way to transfer the simulation to the actual operation. However, there was no template designed for anterior segmental osteotomy so far. The study aimed to introduce and evaluate a set of 3D rapid prototyping surgical templates used in anterior segmental osteotomy. From August 2015 to August 2017, 17 patients with bimaxillary protrusions were recruited and occlusal-based multi-sectional templates were applied in the surgeries. The cephalometric analysis and 3D superimposition were performed to evaluate the differences between the simulations and actual post-operative outcomes. The patients were followed-up for 12 months to evaluate the incidence rate of complications and relapse. Bimaxillary protrusion was corrected in all patients with no complication. In radiographic evaluations, there was no statistically significant difference between the actual operations and the computer-aided 3D simulations (p >0.05, the mean linear and angular differences were less than 1.32mm and 1.72° consequently, and 3D superimposition difference was less than 1.4mm). The Pearson intraclass correlation coefficient reliabilities were high (0.897), and the correlations were highly significant (P< 0.001). The 3D printed surgical template designed in this study can safely and accurately transfer the computer-aided 3D simulation into real practice

The Dual Role of Small Extracellular Vesicles in Joint Osteoarthritis: Their Global and Non-Coding Regulatory RNA Molecule-Based Pathogenic and Therapeutic Effects

OA is the most common joint disease that affects approximately 7% of the global population. Current treatment methods mainly relieve its symptoms with limited repairing effect on joint destructions, which ultimately contributes to the high morbidity rate of OA. Stem cell treatment is a potential regenerative medical therapy for joint repair in OA, but the uncertainty in differentiation direction and immunogenicity limits its clinical usage. Small extracellular vesicles (sEVs), the by-products secreted by stem cells, show similar efficacy levels but have safer regenerative repair effect without potential adverse outcomes, and have recently drawn attention from the broader research community. A series of research works and reviews have been performed in the last decade, providing references for the application of various exogenous therapeutic sEVs for treating OA. However, the clinical potential of target intervention involving endogenous pathogenic sEVs in the treatment of OA is still under-explored and under-discussed. In this review, and for the first time, we emphasize the dual role of sEVs in OA and explain the effects of sEVs on various joint tissues from both the pathogenic and therapeutic aspects. Our aim is to provide a reference for future research in the field

Autosomal Dominant Hypocalcemia (Hypoparathyroidism) Types 1 and 2

Extracellular calcium is essential for life and its concentration in the blood is maintained within a narrow range. This is achieved by a feedback loop that receives input from the calcium-sensing receptor (CASR), expressed on the surface of parathyroid cells. In response to low ionized calcium, the parathyroids increase secretion of parathyroid hormone (PTH) which increases serum calcium. The CASR is also highly expressed in the kidneys, where it regulates the reabsorption of calcium from the primary filtrate. Autosomal dominant hypocalcemia (ADH) type 1 is caused by heterozygous activating mutations in the CASR which increase the sensitivity of the CASR to extracellular ionized calcium. Consequently, PTH synthesis and secretion are suppressed at normal ionized calcium concentrations. Patients present with hypocalcemia, hyperphosphatemia, low magnesium levels, and low or low-normal levels of PTH. Urinary calcium excretion is typically increased due to the decrease in circulating PTH concentrations and by the activation of the renal tubular CASR. Therapeutic attempts using CASR antagonists (calcilytics) to treat ADH are currently under investigation. Recently, heterozygous mutations in the alpha subunit of the G protein G11 (Gα11) have been identified in patients with ADH, and this has been classified as ADH type 2. ADH2 mutations lead to a gain-of-function of Gα11, a key mediator of CASR signaling. Therefore, the mechanism of hypocalcemia appears similar to that of activating mutations in the CASR, namely an increase in the sensitivity of parathyroid cells to extracellular ionized calcium. Studies of activating mutations in the CASR and gain-of-function mutations in Gα11 can help define new drug targets and improve medical management of patients with ADH types 1 and 2

Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation

Hypoparathyroidism (HP) is a disorder characterized by low levels of PTH which lead to hypocalcemia, hyperphosphatemia, and low bone turnover. The most common cause of the disease is accidental removal of the parathyroid glands during thyroid surgery. Novel therapies for HP are needed, but testing them requires reliable animal models of acquired HP. Here, we demonstrate the generation of two mouse models of acquired HP. In the GFP-PTX model, mice with green fluorescent protein (GFP) expressed specifically in the parathyroids (PTHcre-mTmG) were created by crossing PTHcre+ mice with Rosa-mTmGfl/fl mice. Green fluorescing parathyroid glands are easily identified under a fluorescence dissecting microscope and parathyroidectomy is performed in less than 20 min. After fluorescence-guided surgery, mice are profoundly hypocalcemic. Contrary to the traditional thyro-parathyroidectomy, this precise surgical approach leaves thyroid glands and thyroid function intact. The second model, which does not require surgery, is based on a diphtheria-toxin approach. PTHcre-iDTR mice, which express the diphtheria toxin (DT) receptor specifically in the parathyroids, were generated by crossing the inducible DTR mouse with the PTHcre mouse. Parathyroid cells are thus rendered sensitive to diphtheria toxin (DT) and can be selectively destroyed by systemically injecting mice with DT. The resulting hypocalcemic phenotype is stable

Different bone sites-specific response to diabetes rat models: Bone density, histology and microarchitecture.

BACKGROUND AND PURPOSE:Diabetes mellitus (DM) is the most common metabolic disorder that is characterized by hyperglycemia, it can be categorized by T1DM and T2DM. T1DM is also reported to cause bone loss. However, most reports regarding this aspect of T1DM have only investigated a single site; a comparison of bone loss from different areas of the body is still lacking. METHODS:Thirty-five 12-week-old Sprague Dawley® (SD) rats were separated to seven groups. Five rats were euthanized without any surgery at 0 weeks for histological examination and determination of baseline characteristics. In 15 of the rats, DM was induced via Streptozotocin (STZ)-injection, and they were separated to 3 groups (4 weeks, 8 weeks and 12 weeks after STZ-injection). The remaining 15 rats were used as the control group (4 weeks, 8 weeks and 12 weeks after saline-injection). We tested bone-mass loss at four skeletal sites, the tibia, the femur greater trochanter, the spine, and the mandibular bones using micro-computed tomography (CT) and histological tests. RESULTS:Tibia was influenced the most obvious(BV/TV decreased by 27.3%, 52.5%, and 81.2% at 4 weeks, 8 weeks, and 12 weeks, respectively. p<0.05). In contrast, the other three sites were influenced to a lesser extent and bone loss became prominent at a later time point according to the histological and micro-CT tests(Femur: BV/TV did not decrease significantly at the first month or second month. However, and decreased by 49.4% at the third month, P<0.05. Mandible: the BV/TV only decreased by 6.5% at 1 month after STZ-injection. There was still a significant difference between the second and third months. The BV/TV decreased by 47.0% and 68.1% at 2 months and 3 months, respectively, (p<0.05) Spine: the BV/TV only decreased by 6.7%. However, significant change was observed in the spine at the second month and third month after STZ injection. The BV/TV decreased by 45.4% and 64.3%, respectively, p<0.05). CONCLUSION:The results indicate that T1DM can severely influence the bone structure of the 4 skeletal sites. Further, areas with dense trabecular bones were influenced less and at a later time point in comparison to the tibial region. CLINICAL RELEVANCE:Our research can serve as a guide to help increase the success rate of implant treatment, and help decrease the fracture risk in different bone types with greater accuracy

Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends

Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes&mdash;especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future

Additional file 1 of Morphological changes of TMJ disc in surgically treated ADDwoR patients: a retrospective study

Additional file 1. Raw data of TMJ discs of ADDwoR patients

Creating an atlas of the bone microenvironment during oral inflammatory-related bone disease using single-cell profiling

Oral inflammatory diseases such as apical periodontitis are common bacterial infectious diseases that may affect the periapical alveolar bone tissues. A protective process occurs simultaneously with the inflammatory tissue destruction, in which mesenchymal stem cells (MSCs) play a primary role. However, a systematic and precise description of the cellular and molecular composition of the microenvironment of bone affected by inflammation is lacking. In this study, we created a single-cell atlas of cell populations that compose alveolar bone in healthy and inflammatory disease states. We investigated changes in expression frequency and patterns related to apical periodontitis, as well as the interactions between MSCs and immunocytes. Our results highlight an enhanced self-supporting network and osteogenic potential within MSCs during apical periodontitis-associated inflammation. MSCs not only differentiated toward osteoblast lineage cells but also expressed higher levels of osteogenic-related markers, including Sparc and Col1a1. This was confirmed by lineage tracing in transgenic mouse models and human samples from oral inflammatory-related alveolar bone lesions. In summary, the current study provides an in-depth description of the microenvironment of MSCs and immunocytes in both healthy and disease states. We also identified key apical periodontitis-associated MSC subclusters and their biomarkers, which could further our understanding of the protective process and the underlying mechanisms of oral inflammatory-related bone disease. Taken together, these results enhance our understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. We provide these data as a tool for investigators not only to better appreciate the repertoire of progenitors that are stress responsive but importantly to help design new therapeutic targets to restore bone lesions caused by apical periodontitis and other inflammatory-related bone diseases

Additional file 4 of Morphological changes of TMJ disc in surgically treated ADDwoR patients: a retrospective study

Additional file 4. The measurement method of condylar height