Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases.
The purpose of this study was to evaluate the in vitro effects of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and a downregulator of intracellular reactive oxygen species (ROS), on high glucose-induced oxidative stress on tenocytes. Tenocytes from normal Sprague-Dawley rats were cultured in both control and high-glucose conditions. Apocynin was added at cell seeding, dividing the tenocytes into four groups: the control group; regular glucose with apocynin (RG apo+); high glucose with apocynin (HG apo+); and high glucose without apocynin (HG apo–). Reactive oxygen species production, cell proliferation, apoptosis and messenger RNA (mRNA) expression of NOX1 and 4, and interleukin-6 (IL-6) were determined in vitro.Aims
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The aim of this study was to report our experience at 3.5 years with outpatient total hip arthroplasty (THA). In this prospective cohort study, we included all patients who were planned to receive primary THA through the anterior approach between 1 April 2014 and 1 October 2017. Patient-related data and surgical information were recorded. Patient reported outcome measures (PROMs) related to the hip and an anchor question were taken preoperatively, at six weeks, three months, and one year after surgery. All complications, readmissions, and reoperations were registered.Aims
Methods
Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article:
Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol. Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17β-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy.Objectives
Methods
The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy. Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1β to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1β-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1β-induced inflammation.Objectives
Methods
MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined.Objectives
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The aim of this study was to investigate whether clinical and radiological outcomes after intramedullary nailing of displaced fractures of the fifth metacarpal neck using a single thick Kirschner wire (K-wire) are noninferior to those of technically more demanding fixation with two thinner dual wires. This was a multicentre, parallel group, randomized controlled noninferiority trial conducted at 12 tertiary trauma centres in Germany. A total of 290 patients with acute displaced fractures of the fifth metacarpal neck were randomized to either intramedullary single-wire (n = 146) or dual-wire fixation (n = 144). The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire six months after surgery, with a third of the minimal clinically important difference (MCID) used as the noninferiority threshold. Secondary outcomes were pain, health-related quality of life (EuroQol five-dimensional questionnaire (EQ-5D)), radiological measures, functional deficits, and complications.Aims
Patients and Methods
X-linked hypophosphataemic rickets (XLHR) is a disease of impaired bone mineralization characterized by hypophosphataemia caused by renal phosphate wasting. The main clinical manifestations of the disorder are O-shaped legs, X-shaped legs, delayed growth, and bone pain. XLHR is the most common inheritable form of rickets, with an incidence of 1/20 000 in humans. It accounts for approximately 80% of familial cases of hypophosphataemia and serves as the prototype of defective tubular phosphate (PO43+) transport, due to extra renal defects resulting in unregulated The genome DNA samples of all members in the pedigree were extracted from whole blood. We sequenced all exons of the Objectives
Methods
Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb. The medial and lateral cartilage samples of the tibial plateau from 12 osteoarthritis (OA) patients were collected. Ob-Rb messenger RNA (mRNA) was detected in these samples. The Ob-Rb-overexpressing chondrocytes and controls were treated with different doses of leptin for two days. The activation of the p53/p21 pathway and the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells were evaluated. The mammalian target of rapamycin (mTOR) signalling pathway and autophagy were detected after the chondrocytes were treated with a high dose of leptin.Objectives
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Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs.Objectives
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The aim of this study was to identify key pathological genes in osteoarthritis (OA). We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis.Objectives
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Double-level lengthening, bone transport, and bifocal compression-distraction are commonly undertaken using Ilizarov or other fixators. We performed double-level fixator-assisted nailing, mainly for the correction of deformity and lengthening in the same segment, using a straight intramedullary nail to reduce the time in a fixator. A total of 23 patients underwent this surgery, involving 27 segments (23 femora and four tibiae), over a period of ten years. The most common indication was polio in ten segments and rickets in eight; 20 nails were inserted retrograde and seven antegrade. A total of 15 lengthenings were performed in 11 femora and four tibiae, and 12 double-level corrections of deformity without lengthening were performed in the femur. The mean follow-up was 4.9 years (1.1 to 11.4). Four patients with polio had tibial lengthening with arthrodesis of the ankle. We compared the length of time in a fixator and the external fixation index (EFI) with a control group of 27 patients (27 segments) who had double-level procedures with external fixation. The groups were matched for the gain in length, age, and level of difficulty score.Aims
Patients and Methods
The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical A total of 337 647 primary total hip arthroplasties (THAs) from the United Kingdom National Joint Registry (NJR) were included in a multivariable survival and regression analysis to identify the adjusted hazard of revision for periprosthetic fracture following primary THA using a cementless stem. The effect of a collar in cementless THA on this risk was evaluated in an Aims
Materials and Methods
Hip fractures are associated with high morbidity, mortality, and costs. One strategy for improving outcomes is to incentivize hospitals to provide better quality of care. We aimed to determine whether a pay-for-performance initiative affected hip fracture outcomes in England by using Scotland, which did not participate in the scheme, as a control. We undertook an interrupted time series study with data from all patients aged more than 60 years with a hip fracture in England (2000 to 2018) using the Hospital Episode Statistics Admitted Patient Care (HES APC) data set linked to national death registrations. Difference-in-differences (DID) analysis incorporating equivalent data from the Scottish Morbidity Record was used to control for secular trends. The outcomes were 30-day and 365-day mortality, 30-day re-admission, time to operation, and acute length of stay.Aims
Materials and Methods
The aim of this study was to give estimates of the incidence of component incompatibility in hip and knee arthroplasty and to test the effect of an online, real-time compatibility check. Intraoperative barcode registration of arthroplasty implants was introduced in Denmark in 2013. We developed a compatibility database and, from May 2017, real-time compatibility checking was implemented and became part of the registration. We defined four classes of component incompatibility: A-I, A-II, B-I, and B-II, depending on an assessment of the level of risk to the patient (A/B), and on whether incompatibility was knowingly accepted (I/II).Aims
Materials and Methods
Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. Objectives
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Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article:
