MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data. Cite this article:
Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein).Aims
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There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence? A total of 114 patients with a sacral GCT who underwent nerve-sparing surgery at our hospital between July 2005 and August 2017 were reviewed. The rate of local recurrence was determined, and Kaplan-Meier survival analysis carried out to evaluate the mean recurrence-free survival. Possible risks factors including demographics, tumour characteristics, adjuvant therapy, operation, and laboratory indices were analyzed using univariate analysis. Variables with p < 0.100 in the univariate analysis were further considered in a multivariate Cox regression analysis to identify the risk factors.Aims
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The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR.Aims
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Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing. The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series.Aims
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Hospital case volume is shown to be associated with postoperative outcomes in various types of surgery. However, conflicting results of volume-outcome relationship have been reported in hip fracture surgery. This retrospective cohort study aimed to evaluate the association between hospital case volume and postoperative outcomes in patients who had hip fracture surgery. We hypothesized that higher case volume would be associated with lower risk of in-hospital and one-year mortality after hip fracture surgery. Data for all patients who underwent surgery for hip fracture from January 2008 to December 2016 were extracted from the Korean National Healthcare Insurance Service database. According to mean annual case volume of surgery for hip fracture, hospitals were classified into very low (< 30 cases/year), low (30 to 50 cases/year), intermediate (50 to 100 cases/year), high (100 to 150 cases/year), or very high (> 150 cases/year) groups. The association between hospital case volume and in-hospital mortality or one-year mortality was assessed using the logistic regression model to adjust for age, sex, type of fracture, type of anaesthesia, transfusion, comorbidities, and year of surgery.Aims
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Post-traumatic elbow stiffness is a disabling condition that remains challenging for upper limb surgeons. Open elbow arthrolysis is commonly used for the treatment of stiff elbow when conservative therapy has failed. Multiple questions commonly arise from surgeons who deal with this disease. These include whether the patient has post-traumatic stiff elbow, how to evaluate the problem, when surgery is appropriate, how to perform an excellent arthrolysis, what the optimal postoperative rehabilitation is, and how to prevent or reduce the incidence of complications. Following these questions, this review provides an update and overview of post-traumatic elbow stiffness with respect to the diagnosis, preoperative evaluation, arthrolysis strategies, postoperative rehabilitation, and prevention of complications, aiming to provide a complete diagnosis and treatment path. Cite this article:
Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone.Aims
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This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI. Patients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker.Aims
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From November 1994 to March 1997, we harvested 137 grafts of the femoral head from 125 patients for donation during total hip arthroplasty according to the guidelines of the American Associations of Tissue Banks (AATB) and the European Association of Musculo-Skeletal transplantation (EAMST). In addition to the standards recommended by these authorities, we performed histopathological examination of a core biopsy of the retrieved bone allograft and of the synovium. Of the 137 allografts, 48 (35.0%) fulfilled all criteria and were free for donation; 31 (22.6%) were not regarded as suitable for transplantation because the serological retests at six months were not yet complete and 58 (42.3%) were discarded because of incomplete data. Of those discarded, five showed abnormal histopathological findings; three were highly suspicious of low-grade B-cell lymphoma, one of monoclonal plasmacytosis and the other of non-specific
The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL. The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF).Aims
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Wear products of metal implants are known to induce biological events which may have profound consequences for the microcirculation of skeletal muscle. Using the skinfold chamber model and intravital microscopy we assessed microcirculatory parameters in skeletal muscle after confrontation with titanium and stainless-steel wear debris, comparing the results with those of bulk materials. Implantation of stainless-steel bulk and debris led to a distinct activation of leukocytes combined with a disruption of the microvascular endothelial integrity and massive leukocyte extravasation. While animals with bulk stainless steel showed a tendency to recuperation, stainless-steel wear debris induced such severe
Experiments on white mice were undertaken to determine the reaction of bone to the intramedullary introduction of the virus of tick-borne encephalitis. The following conclusions were drawn. 1. The tick-borne encephalitis virus S47, when introduced intraosteally in white mice, provokes osteitis. 2.
Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD. The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between Aims
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During the COVID-19 pandemic, many patients continue to require urgent surgery for hip fractures. However, the impact of COVID-19 on perioperative outcomes in these high-risk patients remains unknown. The objectives of this study were to establish the effects of COVID-19 on perioperative morbidity and mortality, and determine any risk factors for increased mortality in patients with COVID-19 undergoing hip fracture surgery. This multicentre cohort study included 340 COVID-19-negative patients versus 82 COVID-19-positive patients undergoing surgical treatment for hip fractures across nine NHS hospitals in Greater London, UK. Patients in both treatment groups were comparable for age, sex, body mass index, fracture configuration, and type of surgery performed. Predefined perioperative outcomes were recorded within a 30-day postoperative period. Univariate and multivariate analysis were used to identify risk factors associated with increased risk of mortality.Aims
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The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA.Aims
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Femoroacetabular impingement (FAI) is a potential cause of hip osteoarthritis (OA). The purpose of this study was to investigate the expression profile of matrix metalloproteinases (MMPs) in the labral tissue with FAI pathology. In this study, labral tissues were collected from four FAI patients arthroscopically and from three normal hips of deceased donors. Proteins extracted from the FAI and normal labrums were separately applied for MMP array to screen the expression of seven MMPs and three tissue inhibitors of metalloproteinases (TIMPs). The expression of individual MMPs and TIMPs was quantified by densitometry and compared between the FAI and normal labral groups. The expression of selected MMPs and TIMPs was validated and localized in the labrum with immunohistochemistry.Aims
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Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article:
Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold. Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining.Aims
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To explore the effect of different types of articulating antibiotic-loaded cement spacers in two-stage revision for chronic hip prosthetic joint infection (PJI). A retrospective cohort study was performed involving 36 chronic PJI patients treated with different types of articulating antibiotic-loaded cement spacers between January 2014 and December 2017. The incidence of complications and the therapeutic effects of different types of antibiotic-loaded articulating cement spacers were compared.Aims
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