To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
Methods
Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, these focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in Abstract
Objective
Methods
3D printing of synthetic scaffolds mimicking natural bone chemical composition, structure, and mechanical properties is a promising approach for repairing bone injuries. Direct ink writing (DIW), a type of 3D printing, confers compatibility with a wide range of materials without exposing these materials to extreme heat. Optimizing ink properties such as filament formation capabilities, shear-thinning, and high storage modulus recovery would improve DIW fabrication characteristics. In this study, composite inks based on biodegradable polycaprolactone (PCL), reinforced with nano-hydroxyapatite (HAp), and loaded with vancomycin were designed and evaluated for their rheological properties, wettability, mechanical properties, and antimicrobial properties. The formulated composite inks displayed a shear-thinning behaviour exhibited storage modulus recovery percentages above 80% for all formulations, which is essential for extrusion deposition by DIW at room temperature. Ink formulations were able to form fully interconnected lattice scaffolds with porosities ranging from 42% to 65%. Increasing the HAp concentrations from 55% to 85% w/w increased the shear thinning behaviour and reduced the printed filament width to more closely match the nozzle diameter; this indicates higher HAp proportion reduces ink shrinkage. The scaffold had high wettability at HAp proportions above 65% w/w and the compressive elastic modulus of DIW printed scaffolds exhibited within the range of trabecular bone. Antimicrobial activity was apparent from the agar diffusion assay; zones of inhibition ranging from 15.82 ± 0.25 mm and 20.06 ± 0.25 mm were observed after 24 hr for composite scaffolds loaded with 3% and 9% w/w vancomycin respectively. Vancomycin-loaded PCL/HAp composite inks were developed, displaying good printability, wettability, mechanical properties, and antimicrobial properties, making them an attractive choice for bone repair and regeneration. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.Abstract
Declaration of Interest
Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA).Aims
Methods
CT-based three-column classification (TCC) has been widely used in the treatment of tibial plateau fractures (TPFs). In its updated version (updated three-column concept, uTCC), a fracture morphology-based injury mechanism was proposed for effective treatment guidance. In this study, the injury mechanism of TPFs is further explained, and its inter- and intraobserver reliability is evaluated to perfect the uTCC. The radiological images of 90 consecutive TPF patients were collected. A total of 47 men (52.2%) and 43 women (47.8%) with a mean age of 49.8 years (Objectives
Methods
The stable inhibition of miR-214 in the aged osteoporotic rats induced by OVX could be achieved by periodic administration of AntagomiR-214 at a dosage of 4 mg/kg and at an interval of 7 days, which will provide a potential bone anabolic strategy for treatment of osteoprosis. MiR-214 has a crucial role in suppressing bone formation and miR-214 inhibition in osteogenic cells may be a potential anabolic strategy for ameliorating osteoporosis (Wang X, et al. 2013). An aged ovariectomised rat has been regarded as a golden model to test bone anabolic agents for reversing established osteoporosis in aged postmenopausal women (Li X, et al. 2009). However, there is still lack of evidence to demonstrate bone anabolic potential of therapeutic inhibition of miR-214 within osteogenic cells in the golden model. So, it should be necessary to establish RNAi-based administration protocol toward stable inhibition of miR-214 at a low level in the golden model. A targeted delivery system specifically facilitating Antagomir-214 approaching osteogenic cells, Summary Statement
Introduction
Intracapsular and para-articular osteochondromas are a rare subtype of soft tissue chondroma occurring in and around joints. We report a giant 5.5cm × 5.5cm × 3.0cm mass occurring in the knee of a 45 years old lady and examine previous cases to update our understanding of para-articular soft tissue osteochondromas. Clinicopathological data were obtained from medical records for the case report whilst a multi-database literature search was conduction for the literature review. 27 articles containing 39 cases were identified in the English literature under our strict inclusion criteria. Along with our data, 40 cases were collated and analysed to provide a set of reference characteristics. These included: age, male-female ratio, spatial location, time of onset, tumour size, clinical symptoms, mechanism of injury, investigations used, treatment received, histopathology features, follow-up and recurrence characteristics. Statistical analysis was performed on data to elicit any discernable pattern of tumour formation. Median age of patients was 50 years old with a male to female ratio of 1:1.11. Most commonly occurs in the 40s, 50s and 60s accounting for two-thirds of all cases. Majority of tumours were located within or adjacent to a fat pad structure. 33 were located in the infra-patellar region, 3 in the suprapatella/pre-femoral region and 4 in other para-articular locations. Average time of onset to diagnosis was 5.81 yrs with a mean volume of 87.5 cubic centimetres. No discernable correlation between time of onset to diagnosis and tumour size was found (spearman correlation co-efficient 0.534, p=0.007). The main symptom reported was pain in 29 cases, whilst 5 were pain free, 6 cases were unspecified. X-Rays, CT and MRI have become the core imaging modalities in investigation. En bloc excision is the choice of treatment, whilst arthroscopic techniques have also been used with similar success. Histologically, 35 cases had a typical description of a cartilage capped lesion with central trabecular bone and areas of endochondral ossification. 3 cases had a histological appearance of predominantly bone whilst 2 cases had predominantly cartilage. All tumours analysed were benign. No recurrences were reported with an average follow up period of 1.91 years. We have provided the latest set of data for the characterisation of para-articular and intracapsular soft tissue osteochondromas. These tumours are benign entity with an invariably good outcome following simple excision. Recognition of this entity is important to prevent over investigation and the performance unnecessarily invasive and radical procedures.
