Introduction. Osteoarthritis (OA) of the knee, a prevalently degenerative joint disorder provoked by articular cartilage loss, accounts for the leading cause of total knee arthroplasty.
Immune response in periprosthetic joint infection (PJI) is diverse. Resident macrophage and/or wandering monocyte are superb guardians to sense microbial attacks, take invaders and alarm the danger. Neutrophils are refined but momentary fighters to kill microbes with projectile weapons as well as predation. The swift action is usually effective at the forefront to prevent expansion of infectious foci. However, such characteristics often evokes overshooting via self-defeating of pus, thus leading to crucial soft tissue damage in the acute phase. Intervention of monocyte/macrophages follow and act as wise organizers. In addition, stromal fibroblasts also act in front for host defence. They equip innate immune sensors (TLRs, NLRs), which can sense dangers and trigger off inflammatory response, but also is usually self-regulated. These sensors not only interact each other, but also have possible contribution to selective
Aims. Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Methods. Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and
Objectives. 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. Methods. 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
Objectives. Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of
Aims. Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Methods. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and
Chondrocytic activity is downregulated by compromised
Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and
The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff tendon degeneration has focused on its relationship to cell death. The types of cell death known to be associated with rotator cuff tendon degeneration are apoptosis, necrosis, and autophagic cell death. The increased incidence of cell death in degenerative tendon tissue may affect the rates of collagen synthesis and repair, possibly weakening tendon tissue and increasing the risk of tendon rupture. The biomolecular mechanisms of the degenerative changes leading to apoptotic cell death in rotator cuff tenofibroblasts have been identified as oxidative-stress-related cascade mechanisms. Furthermore, apoptosis, necrosis, and autophagic cell death are all known to be mediated by oxidative stress, a condition in which ROS (reactive oxygen species) are overproduced. Lower levels of oxidative stress trigger apoptosis; higher levels mediate necrosis. Although the signaltransduction pathway leading to
Osteoporosis (OP) and osteoarthritis (OA) are leading causes of musculoskeletal dysfunction in elderly, with chondrocyte senescence, inflammation, oxidative stress, subcellular organelle dysfunction, and genomic instability as prominent features. Age-related intestinal disorders and gut dysbiosis contribute to host tissue inflammation and oxidative stress by affecting host immune responses and cell metabolism. Not surprisingly, the development of OP and OA correlate with dysregulations of the gut microflora in rodents and humans. Intestinal microorganisms produce metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide, and liposaccharides, affecting mitochondrial function, metabolism, biogenesis,
Tendon injuries occur frequently in athletes and the general population, with inferior healing leading to deposition of fibrotic scar tissue. New treatments are essential to limit fibrosis and enable tendon regeneration post-injury. In this study, we tested the hypothesis that rapamycin improves tendon repair and limits fibrosis by inhibiting the mTOR pathway. The left hindlimb of female adult Wistar rats was injured by needle puncture and animals were either given daily injections of rapamycin (2mg/kg) or vehicle. Animals were euthanized 1 week or 3 weeks post-injury (n=6/group). Left and right Achilles tendons were harvested, with the right limbs acting as controls. Tendon sections were stained with haematoxylin & eosin, and scored by 2 blinded scorers, assessing alterations in cellularity, cell morphology, vascularity, extracellular matrix (ECM) organization and peritendinous fibrosis. Immunohistochemistry was performed for the tendon pan-vascular marker CD146 and the
Abstract. Objective. The aim of our systematic review was to report the latest evidence on the effects of CoCr particles on local soft tissue with a focus on its clinical relevance. Methods. PubMed, Embase, and Cochrane Library databases were screened to perform an extensive review. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical and preclinical results written in English. Relative data were extracted and critically analyzed. PRISMA guidelines were applied, and the risk of bias was assessed, as was the methodological quality of the included studies. Results. 30 studies were included after applying the inclusion and exclusion criteria. Of these, 24 were preclinical studies (18 in vitro human studies, 6 animal modal studies, including 3 in vitro and 3 in vivo), 5 were clinical studies and 1 was previous review on similar topic. The presence of metal ions causes cell damage by reducing cell viability, inducing DNA damage, and triggering the secretion of cytokines. Mechanisms of apoptosis,
Chondrocyte dysfunction is attributable to the development of osteoarthritis (OA). Deregulation of chondrogenic regulators and deleterious factors, e.g. proteinases, Wnt signalling components, and
Onset and progression of osteoarthritis (OA) is affected by a plethora of factors, including joint injury, obesity, aging, and heredity. This multi-factorial etiology obstructs our understanding of driving molecular mechanisms, which likely comprise an interplay between systemic and local factors. Next to biomechanical factors and cytokines, the course of OA appears to be altered by microenvironmental oxidative stress: cumulative evidence now suggests a prominent participation of cell signalling mediated by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master regulator of cellular protective processes, in this process. Nrf2 activation through phosphorylation of mitogen-activated protein kinases (MAPKs) regulates Nrf2 target genes, like hemeoxygenase-1 (HO-1), superoxide dismutase 2 (SOD2), or NAD(P)H Quinone Dehydrogenase 1 (NQO1) in OA chondrocytes. Maintaining high levels of HO-1 appears to be beneficial against OA development. Experimental manipulation of putative antioxidant response element (ARE) binding sites alters the in vitro expression of key transcription factors of chondrocyte markers in promoter-reporter assays. Potentially, Nrf2 is involved in
We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism. Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.Aims
Methods
Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases.
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.Aims
Methods
Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers.Aims
Methods