The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis

Abstract Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant chondrocyte metabolism is a response to changes in the inflammatory microenvironment and may play a key role in cartilage degeneration and OA progression. Under conditions of environmental stress, chondrocytes tend to adapt their metabolism to microenvironmental changes by shifting from one metabolic pathway to another, for example from oxidative phosphorylation to glycolysis. Similar changes occur in other joint cells, including synoviocytes. Switching between these pathways is implicated in metabolic alterations that involve mitochondrial dysfunction, enhanced anaerobic glycolysis, and altered lipid and amino acid metabolism. The shift between oxidative phosphorylation and glycolysis is mainly regulated by the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways. Chondrocyte metabolic changes are likely to be a feature of different OA phenotypes. Determining the role of chondrocyte metabolism in OA has revealed key features of disease pathogenesis. Future research should place greater emphasis on immunometabolism and altered metabolic pathways as a means to understand the pathophysiology of age-related OA. This knowledge will advance the development of new drugs against therapeutic targets of metabolic significance

Surgical management of an enormous subgaleal hematoma accompanying occipital bone's destruction in a 30 years old man with a history of hemophilia A

Enormous enormous subgaleal hematoma with epidural extension, accompanying occipital bone's absorption is an uncommon complication of hemophilia A. A 30 years old man presenting scalp lump was found enormous enormous subgaleal hematoma with epidural extension, accompanying occipital bone's destruction by computed tomography (CT) scan, and laboratory examination indicated that the concentration of his factor VII was 2% of normal level. Further inquiring his medical history found that this patient has been suffering from hemophilia A diagnosed when he was 6 years old. He recovered well after receiving the therapertic methods of factor VII replacement and surgical decompression. This case tells us that patient suffering from enormous enormous subgaleal hematoma with epidural extension, accompanying occipital bone's destruction and hemophilia A could recover well as long as he is well treated. Keywords: Neurosurgery, Factor VII, Enormous subgaleal hematoma with epidural extension, occipital bone's destruction, Hemophilia

High Pressure Polymerization of 2,6-Diethynylpyridine

Pressure induced polymerization (PIP) of unsaturated molecules like aromatics is highly focused on its production of novel carbon materials like diamond nanothread and graphane. However, the high stability of the aromatic molecules results in a high polymerization pressure at room temperature. To reduce the reaction pressure of the aromatic ring, here we introduced conjugated alkynyl, investigated the PIP of 2,6-diethynylpyridine (2,6-DEP) up to 30.7 GPa, and successfully obtained one-dimensional (1-D) ordered polymers below 10 GPa. In situ Raman and IR spectra show that the alkynyl starts to react at 4–5 GPa. At 5.4 GPa, the critical crystal structure of 2,6-DEP was investigated by in situ X-ray diffraction, and the shortest intermolecular distance was determined as 2.90 Å, between the pyridine ring. The product recovered from 10 GPa shows clearly a 1-D structure via transmission electron microscopy (TEM), and strong diffractions at d = 7.5 and 5.2 Å, corresponding to the interplane distance of the stacked 1-D polymer. Theoretical simulations show that the reaction starts between the alkynyl groups, after which the aromatic rings are drawn close to each other and react. Combining the predicted reaction and the experimental result, we concluded possible models of the product. Our study shows that alkynyl is a good initiator for reducing the polymerization pressure of the aromatics and therefore allows the synthesis of ordered 1-D carbon materials in large scale

Association of thyroid hormone with osteoarthritis: from mendelian randomization and RNA sequencing analysis

Abstract Background The relationship between thyroid hormone (TH) levels in vivo and osteoarthritis (OA) remains inconclusive. This study aims to investigate the association between TH levels and OA, analyze the effect of triiodothyronine on hypertrophic chondrocyte differentiation and OA progression, and identify potential target genes of triiodothyronine in OA to evaluate its diagnostic value. Methods Two-sample mendelian randomization method was used to probe the causal links between hyperthyroidism and OA. Differentially expressed genes (DEGs) from two RNA-sequencing data in Gene Expression Omnibus (GSE199847 and GSE114007) and enrichment analysis of DEGs (166 commonly upregulated genes and 71 commonly downregulated genes of GSE199847 and GSE114007) was performed to analyze the effect of triiodothyronine (T3) on hypertrophic chondrocyte differentiation and OA. C28/I2 cells treated with T3 and reverse transcription and quantitative real-time polymerase chain reaction were used to validate T3 targeted genes. The diagnostic performance of target genes was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results There was a positive causal association between hyperthyroidism and OA (IVW result, OR = 1.330, 95% CI 1.136–1.557, P = 0.0004). Weighted median and Weighted mode analysis also demonstrated that hyperthyroidism had a positive causal association with OA (p  1). Bioinformatics analysis indicated T3 can partially induce the emergence of late hypertrophic chondrocyte and promote OA through extracellular matrix organization, blood vessel development, skeletal system development and ossification. Post-T3 treatment, MAFB, C1QTNF1, COL3A1 and ANGPTL2 were significantly elevated in C28/I2 cells. ROC curves in GSE114007 showed that AUC of all above genes were ≥ 0.7. Conclusions This study identified that hyperthyroidism has a positive causal association with OA by MR analysis. T3 induced hypertrophic chondrocytes promote OA progression by upregulating genes such as MAFB, C1QTNF1, COL3A1 and ANGPTL2, which can also serve as OA diagnosis

Additional file 1 of Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study

Additional file 1: Supplementary 1. Risk of osteoarthritis according to metabolic syndrome and components. Supplementary 2. Associations of genetic risk with OA. Supplementary 3. Sensitive analysis lag for 4 years