Osteoarthritis (OA) is characterized by persistent destruction of articular cartilage. It has been found that microRNAs (miRNAs) are closely related to the occurrence and development of OA. The purpose of the present study was to investigate the mechanism of miR-486 in the development and progression of OA. The expression levels of miR-486 in cartilage were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN), matrix metalloproteinase (MMP)-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) in SW1353 cells at both messenger RNA (mRNA) and protein levels was determined by qRT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Double luciferase reporter gene assay, qRT-PCR, and western blot assay were used to determine whether silencing information regulator 6 (SIRT6) was involved in miR-486 induction of chondrocyte-like cells to a more catabolic phenotype.Aims
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We report a retrospective review of 62 consecutive patients who had a vascularised fibular transfer to reconstruct a large skeletal defect. We were particularly interested in the bone dynamics of the vascularised graft, since fractures occurred in 25% of the cases at an average time of eight months after surgery. Hypertrophy was more common when the limb was mechanically loaded; it was enhanced where the graft was not bypassed by internal fixation. The length of the graft and the use of additional bone graft material had no influence on the incidence of stress fracture or on hypertrophy. We conclude that a vascularised graft should be protected against fatigue fracture during the first year, and that a gradual increase in
We have determined whether somatosensory evoked potentials (SEPs) were detectable after direct mechanical stimulation of normal, injured and reconstructed anterior cruciate ligaments (ACLs) during arthroscopy. We investigated the position sense of the knee before and after reconstruction, and correlated the SEP with instability. Reproducible SEPs were detected in all 19 normal ACLs and in 36 of 38 ACLs reconstructed during a period of 13 months. Of the 45 injured ACLs, reproducible SEPs were detected in 26. The mean difference in anterior displacement in the SEP-positive group of the injured ACL group was significantly lower than that in the SEP-negative group. In the reconstructed group, the postoperative position sense was significantly better than the preoperative position sense. Our results indicate not only that sensory reinnervation occurs in the reconstructed ACL, but also that the response to
Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However,
The aetiologies of common degenerative spine, hip, and knee pathologies are still not completely understood. Mechanical theories have suggested that those diseases are related to sagittal pelvic morphology and spinopelvic-femoral dynamics. The link between the most widely used parameter for sagittal pelvic morphology, pelvic incidence (PI), and the onset of degenerative lumbar, hip, and knee pathologies has not been studied in a large-scale setting. A total of 421 patients from the Cohort Hip and Cohort Knee (CHECK) database, a population-based observational cohort, with hip and knee complaints < 6 months, aged between 45 and 65 years old, and with lateral lumbar, hip, and knee radiographs available, were included. Sagittal spinopelvic parameters and pathologies (spondylolisthesis and degenerative disc disease (DDD)) were measured at eight-year follow-up and characteristics of hip and knee osteoarthritis (OA) at baseline and eight-year follow-up. Epidemiology of the degenerative disorders and clinical outcome scores (hip and knee pain and Western Ontario and McMaster Universities Osteoarthritis Index) were compared between low PI (< 50°), normal PI (50° to 60°), and high PI (> 60°) using generalized estimating equations.Aims
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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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Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article:
Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.
As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells. Cite this article:
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:
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:
Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition. Seven databases were searched for studies of HS and ACDF from inception of the study to 1 September 2019. Both random-effects and fixed-effects models were used to evaluate the overall effect of the C2-C7 range of motion (ROM), ROM of superior/inferior adjacent levels, adjacent segment degeneration (ASD), heterotopic ossification (HO), complications, neck disability index (NDI) score, visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Odom’s criteria, blood loss, and operating and hospitalization time. To obtain more credible results contour-enhanced funnel plots, Egger’s and Begg’s tests, meta-regression, and sensitivity analyses were performed.Aims
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Accurate estimations of the risk of fracture due to metastatic bone disease in the femur is essential in order to avoid both under-treatment and over-treatment of patients with an impending pathological fracture. The purpose of the current retrospective in vivo study was to use CT-based finite element analyses (CTFEA) to identify a clear quantitative differentiating factor between patients who are at imminent risk of fracturing their femur and those who are not, and to identify the exact location of maximal weakness where the fracture is most likely to occur. Data were collected on 82 patients with femoral metastatic bone disease, 41 of whom did not undergo prophylactic fixation. A total of 15 had a pathological fracture within six months following the CT scan, and 26 were fracture-free during the five months following the scan. The Mirels score and strain fold ratio (SFR) based on CTFEA was computed for all patients. A SFR value of 1.48 was used as the threshold for a pathological fracture. The sensitivity, specificity, positive, and negative predicted values for Mirels score and SFR predictions were computed for nine patients who fractured and 24 who did not, as well as a comparison of areas under the receiver operating characteristic curves (AUC of the ROC curves).Aims
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Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF.Aims
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The aim of this study was to describe implant and patient-reported outcome in patients with a unilateral transfemoral amputation (TFA) treated with a bone-anchored, transcutaneous prosthesis. In this cohort study, all patients with a unilateral TFA treated with the Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) implant system in Sahlgrenska University Hospital, Gothenburg, Sweden, between January 1999 and December 2017 were included. The cohort comprised 111 patients (78 male (70%)), with a mean age 45 years (17 to 70). The main reason for amputation was trauma in 75 (68%) and tumours in 23 (21%). Patients answered the Questionnaire for Persons with Transfemoral Amputation (Q-TFA) before treatment and at two, five, seven, ten, and 15 years’ follow-up. A prosthetic activity grade was assigned to each patient at each timepoint. All mechanical complications, defined as fracture, bending, or wear to any part of the implant system resulting in removal or change, were recorded.Aims
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To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways.Aims
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The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.Objectives
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The aim of this study was to systematically review the literature for evidence of the effect of a high-fat diet (HFD) on the onset or progression of osteoarthritis (OA) in mice. A literature search was performed in PubMed, Embase, Web of Science, and Scopus to find all studies on mice investigating the effects of HFD or Western-type diet on OA when compared with a control diet (CD). The primary outcome was the determination of cartilage loss and alteration. Secondary outcomes regarding local and systemic levels of proteins involved in inflammatory processes or cartilage metabolism were also examined when reported.Aims
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